X-108440157-GC-TT

Position:

• chrX-108440157-GC-TT

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The NM_033380.3(COL4A5):​c.32_33delinsTT​(p.Gly11Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency: Genomes: not found (cov: 20)
• Consequence: COL4A5 NM_033380.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.31

Genes affected

COL4A5 (HGNC:2207): (collagen type IV alpha 5 chain) This gene encodes one of the six subunits of type IV collagen, the major structural component of basement membranes. Mutations in this gene are associated with X-linked Alport syndrome, also known as hereditary nephritis. Like the other members of the type IV collagen gene family, this gene is organized in a head-to-head conformation with another type IV collagen gene so that each gene pair shares a common promoter. Alternatively spliced transcript variants have been identified for this gene. [provided by RefSeq, Aug 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL4A5	NM_033380.3	c.32_33delinsTT	p.Gly11Val	missense_variant	1/53	ENST00000328300.11	NP_203699.1
COL4A5	NM_000495.5	c.32_33delinsTT	p.Gly11Val	missense_variant	1/51		NP_000486.1
COL4A5	XM_047441811.1	c.32_33delinsTT	p.Gly11Val	missense_variant	1/42		XP_047297767.1
COL4A5	XM_047441810.1	c.-345_-344delinsTT		5_prime_UTR_variant	1/54		XP_047297766.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL4A5	ENST00000328300.11	c.32_33delinsTT	p.Gly11Val	missense_variant	1/53	1	NM_033380.3	ENSP00000331902

Frequencies

GnomAD3 genomes Cov.: 20

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 20

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Oct 19, 2022

This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 11 of the COL4A5 protein (p.Gly11Val). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with COL4A5-related conditions. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-107683387;