X-108597527-C-A

Variant names:

• chrX-108597527-C-A
• NM_033380.3:c.1738C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_033380.3(COL4A5):​c.1738C>A​(p.Gln580Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000911 in 1,097,575 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 21)
  • Exomes 𝑓: 9.1e-7 (0 hom. 0 hem.)
• Consequence: COL4A5 NM_033380.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.00

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.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23895097).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL4A5	NM_033380.3	c.1738C>A	p.Gln580Lys	missense_variant	Exon 24 of 53	ENST00000328300.11	NP_203699.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL4A5	ENST00000328300.11	c.1738C>A	p.Gln580Lys	missense_variant	Exon 24 of 53	1	NM_033380.3	ENSP00000331902.7
COL4A5	ENST00000483338.1	c.562C>A	p.Gln188Lys	missense_variant	Exon 8 of 20	1		ENSP00000495685.1
COL4A5	ENST00000361603.7	c.1738C>A	p.Gln580Lys	missense_variant	Exon 24 of 51	2		ENSP00000354505.2

Frequencies

GnomAD3 genomes Cov.: 21

GnomAD4 exome AF: 9.11e-7 AC: 1 AN: 1097575 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 363077

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000119

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 21

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.060	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	16
DANN	Benign	0.96
DEOGEN2	Benign	0.087	.;T;T
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.71	T;T;T
M_CAP	Pathogenic	0.35	D
MetaRNN	Benign	0.24	T;T;T
MetaSVM	Benign	-0.68	T
MutationAssessor	Benign	-0.23	N;N;.
PrimateAI	Benign	0.45	T
PROVEAN	Benign	0.15	N;N;.
REVEL	Benign	0.23
Sift	Benign	0.34	T;T;.
Sift4G	Benign	0.82	T;T;.
Polyphen		0.0	.;B;B
Vest4		0.15
MutPred		0.45		Gain of ubiquitination at Q580 (P = 0.009);Gain of ubiquitination at Q580 (P = 0.009);.;
MVP		0.67
MPC		0.38
ClinPred		0.41	T
GERP RS		4.7
Varity_R		0.18
gMVP		0.40

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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-107840757;