NM_000390.4(CHM):c.130G>T (p.Gly44Ter) AND not provided

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Dec 25, 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:: RCV000259262.2

Allele description

NM_000390.4(CHM):c.130G>T (p.Gly44Ter)

Gene:

CHM:CHM Rab escort protein [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

Xq21.2

Genomic location:

Preferred name:

NM_000390.4(CHM):c.130G>T (p.Gly44Ter)

HGVS:

NC_000023.11:g.85981796C>A
NG_009874.2:g.70767G>T
NM_000390.3:c.130G>T
NM_000390.4:c.130G>TMANE SELECT
NM_001145414.4:c.130G>T
NM_001320959.1:c.-315G>T
NM_001362517.1:c.-315G>T
NM_001362518.2:c.-311G>T
NM_001362519.1:c.-311G>T
NP_000381.1:p.Gly44Ter
NP_001138886.1:p.Gly44Ter
LRG_699t1:c.130G>T
LRG_699:g.70767G>T
NC_000023.10:g.85236800C>A
NM_000390.2:c.130G>T

Protein change:

G44*

Links:

dbSNP: rs886041175

NCBI 1000 Genomes Browser:

rs886041175

Molecular consequence:

NM_001320959.1:c.-315G>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001362517.1:c.-315G>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001362518.2:c.-311G>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001362519.1:c.-311G>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_000390.4:c.130G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001145414.4:c.130G>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000329289	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Pathogenic (Aug 17, 2016)	germline	clinical testing	Citation Link,
SCV004300135	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 25, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 9067750, 23811034, 12203991, 30297895, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000329289

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Pathogenic
(Aug 17, 2016)

germline

clinical testing

Citation Link,

SCV004300135

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 25, 2023)

germline

clinical testing

PubMed (5)
[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	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Molecular basis of choroideremia (CHM): mutations involving the Rab escort protein-1 (REP-1) gene.

van den Hurk JA, Schwartz M, van Bokhoven H, van de Pol TJ, Bogerd L, Pinckers AJ, Bleeker-Wagemakers EM, Pawlowitzki IH, Rüther K, Ropers HH, Cremers FP.

Hum Mutat. 1997;9(2):110-7. Review.

PubMed [citation]

PMID:: 9067750

A clinical molecular genetic service for United Kingdom families with choroideraemia.

Ramsden SC, O'Grady A, Fletcher T, O'Sullivan J, Hart-Holden N, Barton SJ, Hall G, Moore AT, Webster AR, Black GC.

Eur J Med Genet. 2013 Aug;56(8):432-8. doi: 10.1016/j.ejmg.2013.06.003. Epub 2013 Jun 25.

PubMed [citation]

PMID:: 23811034

See all PubMed Citations (5)

Details of each submission

From GeneDx, SCV000329289.6

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

Description

The G44X nonsense variant, also reported as c.160 G>T using alternative nomenclature, in the CHM gene has been reported previously in association with choroideremia and was shown to result in complete lack of CHM protein expression in leukocytes (Zhang et al., 2015; McTaggart et al., 2002). This pathogenic variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. Additionally the G44X variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI ExomeSequencing Project, indicating it is not a common benign variant in these populations. Therefore, the G44X variant is interpreted as 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

From Invitae, SCV004300135.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This sequence change creates a premature translational stop signal (p.Gly44*) in the CHM gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CHM are known to be pathogenic (PMID: 9067750, 23811034). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with choroideremia (PMID: 12203991, 30297895). This variant is also known as c.160G>T. ClinVar contains an entry for this variant (Variation ID: 279771). For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: May 12, 2024

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