NM_178014.4(TUBB):c.1201G>A (p.Glu401Lys) AND Multiple benign circumferential skin creases on limbs 1

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Feb 23, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV002274914.3

Allele description [Variation Report for NM_178014.4(TUBB):c.1201G>A (p.Glu401Lys)]

NM_178014.4(TUBB):c.1201G>A (p.Glu401Lys)

Gene:

TUBB:tubulin beta class I [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

6p21.33

Genomic location:

Preferred name:

NM_178014.4(TUBB):c.1201G>A (p.Glu401Lys)

HGVS:

NC_000006.12:g.30724263G>A
NG_034142.1:g.9063G>A
NM_001293212.2:c.1261G>A
NM_001293213.2:c.595G>A
NM_001293214.2:c.1069G>A
NM_001293215.2:c.985G>A
NM_001293216.2:c.985G>A
NM_178014.4:c.1201G>AMANE SELECT
NP_001280141.1:p.Glu421Lys
NP_001280142.1:p.Glu199Lys
NP_001280143.1:p.Glu357Lys
NP_001280144.1:p.Glu329Lys
NP_001280145.1:p.Glu329Lys
NP_821133.1:p.Glu401Lys
NC_000006.11:g.30692040G>A
NM_178014.2:c.1201G>A
NM_178014.3:c.1201G>A
NR_120608.2:n.757G>A
P07437:p.Glu401Lys

Protein change:

E199K; GLU401LYS

Links:

UniProtKB: P07437#VAR_071765; OMIM: 191130.0003; dbSNP: rs587777357

NCBI 1000 Genomes Browser:

rs587777357

Molecular consequence:

NM_001293212.2:c.1261G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001293213.2:c.595G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001293214.2:c.1069G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001293215.2:c.985G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001293216.2:c.985G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_178014.4:c.1201G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_120608.2:n.757G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Multiple benign circumferential skin creases on limbs 1
Synonyms:: Skin creases, multiple benign ring-shaped, of limbs; Kunze Riehm syndrome; CIRCUMFERENTIAL SKIN CREASES, KUNZE TYPE; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0020738; MedGen: C4551592; OMIM: 156610

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Homo sapiens acyl-CoA synthetase long chain family member 6 (ACSL6), transcript ...
Homo sapiens acyl-CoA synthetase long chain family member 6 (ACSL6), transcript variant 4, mRNA
gi|1676318039|ref|NM_001205248.2|

Nucleotide
Mus musculus zinc finger protein 13 (Zfp13), transcript variant 7, mRNA
Mus musculus zinc finger protein 13 (Zfp13), transcript variant 7, mRNA
gi|2329567201|ref|NM_001414208.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002562206	Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Aug 16, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV003841998	3billion	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Feb 23, 2023)	unknown	clinical testing	PubMed (2) [See all records that cite these PMIDs] 23246003, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002562206

Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Aug 16, 2022)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV003841998

3billion

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Feb 23, 2023)

unknown

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	unknown	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Mutations in the β-tubulin gene TUBB5 cause microcephaly with structural brain abnormalities.

Breuss M, Heng JI, Poirier K, Tian G, Jaglin XH, Qu Z, Braun A, Gstrein T, Ngo L, Haas M, Bahi-Buisson N, Moutard ML, Passemard S, Verloes A, Gressens P, Xie Y, Robson KJ, Rani DS, Thangaraj K, Clausen T, Chelly J, Cowan NJ, et al.

Cell Rep. 2012 Dec 27;2(6):1554-62. doi: 10.1016/j.celrep.2012.11.017. Epub 2012 Dec 13.

PubMed [citation]

PMID:: 23246003
PMCID:: PMC3595605

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen, SCV002562206.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From 3billion, SCV003841998.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

The variant is not observed in the gnomAD v2.1.1 dataset. Missense changes are a common disease-causing mechanism. In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.77; 3Cnet: 0.93). Same nucleotide change resulting in same amino acid change has been previously reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000127191). The variant has been previously reported as de novo in a similarly affected individual (PMID: 23246003). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Nov 3, 2024

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