Variant 3-99795504-C-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_020351.4(COL8A1):c.1603C>G(p.Pro535Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000697 in 1,434,904 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

COL8A1
NM_020351.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.87

Variant links:

Genes affected

COL8A1 (HGNC:2215): (collagen type VIII alpha 1 chain) This gene encodes one of the two alpha chains of type VIII collagen. The gene product is a short chain collagen and a major component of the basement membrane of the corneal endothelium. The type VIII collagen fibril can be either a homo- or a heterotrimer. Alternatively spliced transcript variants encoding the same protein have been observed. [provided by RefSeq, Dec 2011]

COL8A1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL8A1	NM_020351.4 link	c.1603C>G	p.Pro535Ala	missense_variant	4/4	ENST00000652472.1	NP_065084.2	P27658
COL8A1	NM_001850.5 link	c.1603C>G	p.Pro535Ala	missense_variant	5/5		NP_001841.2	P27658

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
COL8A1	ENST00000652472.1 link	c.1603C>G	p.Pro535Ala	missense_variant	4/4		NM_020351.4	ENSP00000498483.1	P27658
COL8A1	ENST00000261037.7 link	c.1603C>G	p.Pro535Ala	missense_variant	5/5	1		ENSP00000261037.3	P27658
COL8A1	ENST00000273342.8 link	c.1603C>G	p.Pro535Ala	missense_variant	4/4	2		ENSP00000273342.3	P27658

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.97e-7

AC:

AN:

1434904

Hom.:

Cov.:

AF XY:

0.00000141

AC XY:

AN XY:

711390

show subpopulations

Gnomad4 AFR exome

AF:

0.0000305

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000189

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 03, 2021

The c.1603C>G (p.P535A) alteration is located in exon 5 (coding exon 2) of the COL8A1 gene. This alteration results from a C to G substitution at nucleotide position 1603, causing the proline (P) at amino acid position 535 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.061

BayesDel_addAF

Uncertain

0.14

BayesDel_noAF

Uncertain

-0.030

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Uncertain

0.58

D;D

Eigen

Uncertain

0.47

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Uncertain

0.87

LIST_S2

Uncertain

0.95

.;D

M_CAP

Uncertain

0.11

MetaRNN

Uncertain

0.53

D;D

MetaSVM

Uncertain

0.68

MutationAssessor

Uncertain

2.4

M;M

PrimateAI

Uncertain

0.71

PROVEAN

Benign

-1.7

N;N

REVEL

Uncertain

0.52

Sift

Benign

0.088

T;T

Sift4G

Uncertain

0.020

D;D

Polyphen

0.90

P;P

Vest4

0.44

MutPred

0.52

Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);

MVP

0.95

MPC

0.22

ClinPred

0.47

GERP RS

5.8

Varity_R

0.079

gMVP

0.51

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over