X-108626284-C-G

Variant names:

• chrX-108626284-C-G
• NM_033380.3:c.3181C>G

Variant summary

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

The NM_033380.3(COL4A5):​c.3181C>G​(p.Gln1061Glu) 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 1,097,168 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes 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: 22)
  • Exomes 𝑓: 9.1e-7 (0 hom. 1 hem.)
• Consequence: COL4A5 NM_033380.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.211

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=0.21133593).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL4A5	NM_033380.3	c.3181C>G	p.Gln1061Glu	missense_variant	Exon 36 of 53	ENST00000328300.11	NP_203699.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL4A5	ENST00000328300.11	c.3181C>G	p.Gln1061Glu	missense_variant	Exon 36 of 53	1	NM_033380.3	ENSP00000331902.7
COL4A5	ENST00000483338.1	c.2005C>G	p.Gln669Glu	missense_variant	Exon 20 of 20	1		ENSP00000495685.1
COL4A5	ENST00000361603.7	c.3181C>G	p.Gln1061Glu	missense_variant	Exon 36 of 51	2		ENSP00000354505.2
COL4A5	ENST00000505728.1	c.412C>G	p.Gln138Glu	missense_variant	Exon 4 of 5	3		ENSP00000424137.1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome AF: 9.11e-7 AC: 1 AN: 1097168 Hom.: 0 Cov.: 30 AF XY: 0.00000276 AC XY: 1 AN XY: 362710

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: 0.0000185

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.021	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	14
DANN	Benign	0.52
DEOGEN2	Benign	0.33	.;T;T
FATHMM_MKL	Benign	0.33	N
LIST_S2	Benign	0.63	T;T;T
M_CAP	Pathogenic	0.58	D
MetaRNN	Benign	0.21	T;T;T
MetaSVM	Benign	-0.50	T
MutationAssessor	Benign	-0.61	N;N;.
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.70	N;N;.
REVEL	Benign	0.27
Sift	Benign	1.0	T;T;.
Sift4G	Benign	1.0	T;T;.
Polyphen		0.42	.;B;B
Vest4		0.23
MutPred		0.30		Loss of stability (P = 0.1976);Loss of stability (P = 0.1976);.;
MVP		0.79
MPC		0.32
ClinPred		0.40	T
GERP RS		4.8
Varity_R		0.25
gMVP		0.56

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-107869514;