NM_016038.4(SBDS):c.388G>A (p.Val130Met) AND Shwachman-Diamond syndrome 1

Germline classification:: Likely pathogenic (2 submissions)
Last evaluated:: Feb 14, 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:: RCV000987894.3

Allele description [Variation Report for NM_016038.4(SBDS):c.388G>A (p.Val130Met)]

NM_016038.4(SBDS):c.388G>A (p.Val130Met)

Gene:

SBDS:SBDS ribosome maturation factor [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

7q11.21

Genomic location:

Preferred name:

NM_016038.4(SBDS):c.388G>A (p.Val130Met)

Other names:

p.Val130Met

HGVS:

NC_000007.14:g.66993288C>T
NG_007277.1:g.7314G>A
NG_033069.1:g.1484C>T
NM_016038.4:c.388G>AMANE SELECT
NP_057122.2:p.Val130Met
LRG_104t1:c.388G>A
LRG_104:g.7314G>A
NC_000007.13:g.66458275C>T
NM_016038.2:c.388G>A

Protein change:

V130M

Links:

dbSNP: rs201070132

NCBI 1000 Genomes Browser:

rs201070132

Molecular consequence:

NM_016038.4:c.388G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Shwachman-Diamond syndrome 1 (SDS1)
Identifiers:: MONDO: MONDO:0044204; MedGen: C4692625; OMIM: 260400

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001137384	Mendelics	criteria provided, single submitter (Mendelics Assertion Criteria 2017)	Likely pathogenic (May 28, 2019)	unknown	clinical testing	Citation Link,
SCV004175813	Neuberg Centre For Genomic Medicine, NCGM	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Feb 14, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001137384

Mendelics

criteria provided, single submitter

(Mendelics Assertion Criteria 2017)

Likely pathogenic
(May 28, 2019)

unknown

clinical testing

Citation Link,

SCV004175813

Neuberg Centre For Genomic Medicine, NCGM

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Feb 14, 2023)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	unknown	unknown	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

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 Mendelics, SCV001137384.1

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

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

From Neuberg Centre For Genomic Medicine, NCGM, SCV004175813.1

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

Description

The missense variant c.388G>A (p.Val130Met) in the SBDS gene has been reported previously in a heterozygous state in patients affected with neuroblastoma (Wu et al., 2022; Bonfiglio et al., 2023). This variant is reported with the allele frequency (0.008%) in the gnomAD Exomes and novel (not in any individuals) in 1000 Genomes. It is submitted to ClinVar as Likely Pathogenic. The amino acid Valine at position 130 is changed to a Methionine changing protein sequence and it might alter its composition and physico-chemical properties. The variant is predicted as damaging by SIFT. The amino acid change p.Val130Met in SBDS is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Likely Pathogenic.

#	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

Last Updated: Apr 6, 2024

ClinVar

Relating variation to medicine