Variant rs201817918 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_015719.4(COL5A3):c.4742G>T(p.Gly1581Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,456,736 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

COL5A3
NM_015719.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.95

Variant links:

Genes affected

COL5A3 (HGNC:14864): (collagen type V alpha 3 chain) This gene encodes an alpha chain for one of the low abundance fibrillar collagens. Fibrillar collagen molecules are trimers that can be composed of one or more types of alpha chains. Type V collagen is found in tissues containing type I collagen and appears to regulate the assembly of heterotypic fibers composed of both type I and type V collagen. This gene product is closely related to type XI collagen and it is possible that the collagen chains of types V and XI constitute a single collagen type with tissue-specific chain combinations. Mutations in this gene are thought to be responsible for the symptoms of a subset of patients with Ehlers-Danlos syndrome type III. Messages of several sizes can be detected in northern blots but sequence information cannot confirm the identity of the shorter messages. [provided by RefSeq, Jul 2008]

COL5A3 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.89

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL5A3	NM_015719.4 link	c.4742G>T	p.Gly1581Val	missense_variant	Exon 64 of 67	ENST00000264828.4	NP_056534.2	P25940
COL5A3	XM_011528042.3 link	c.4739G>T	p.Gly1580Val	missense_variant	Exon 64 of 67		XP_011526344.1
COL5A3	XM_017026849.2 link	c.2405G>T	p.Gly802Val	missense_variant	Exon 37 of 40		XP_016882338.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL5A3	ENST00000264828.4 link	c.4742G>T	p.Gly1581Val	missense_variant	Exon 64 of 67	1	NM_015719.4	ENSP00000264828.3		P25940

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000406

AC:

AN:

246540

Hom.:

AF XY:

0.00

AC XY:

AN XY:

133232

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000293

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.86e-7

AC:

AN:

1456736

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

724178

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000226

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.39

BayesDel_addAF

Uncertain

0.088

BayesDel_noAF

Uncertain

-0.030

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.41

Eigen

Uncertain

0.53

Eigen_PC

Uncertain

0.39

FATHMM_MKL

Benign

0.74

LIST_S2

Pathogenic

0.99

M_CAP

Uncertain

0.19

MetaRNN

Pathogenic

0.89

MetaSVM

Pathogenic

0.94

MutationAssessor

Pathogenic

3.5

PrimateAI

Uncertain

0.61

PROVEAN

Pathogenic

-6.4

REVEL

Pathogenic

0.73

Sift

Uncertain

0.0080

Sift4G

Uncertain

0.0020

Polyphen

1.0

Vest4

0.57

MutPred

0.87

Gain of relative solvent accessibility (P = 0.09);

MVP

0.91

MPC

0.44

ClinPred

0.88

GERP RS

4.2

Varity_R

0.50

gMVP

0.83

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over