chr3-99795004-C-T

Position:

• chr3-99795004-C-T

Variant summary

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

The NM_020351.4(COL8A1):​c.1103C>T​(p.Pro368Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: COL8A1 NM_020351.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.11

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]

ACMG classification

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	c.1103C>T	p.Pro368Leu	missense_variant	4/4	ENST00000652472.1	NP_065084.2
COL8A1	NM_001850.5	c.1103C>T	p.Pro368Leu	missense_variant	5/5		NP_001841.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL8A1	ENST00000652472.1	c.1103C>T	p.Pro368Leu	missense_variant	4/4		NM_020351.4	ENSP00000498483.1
COL8A1	ENST00000261037.7	c.1103C>T	p.Pro368Leu	missense_variant	5/5	1		ENSP00000261037.3
COL8A1	ENST00000273342.8	c.1103C>T	p.Pro368Leu	missense_variant	4/4	2		ENSP00000273342.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 14, 2024

The c.1103C>T (p.P368L) alteration is located in exon 5 (coding exon 2) of the COL8A1 gene. This alteration results from a C to T substitution at nucleotide position 1103, causing the proline (P) at amino acid position 368 to be replaced by a leucine (L). 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	0.087
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.69	D;D
Eigen	Benign	0.18
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.90	.;D
M_CAP	Uncertain	0.17	D
MetaRNN	Uncertain	0.60	D;D
MetaSVM	Uncertain	0.71	D
MutationAssessor	Uncertain	2.3	M;M
PrimateAI	Uncertain	0.63	T
PROVEAN	Pathogenic	-5.3	D;D
REVEL	Uncertain	0.50
Sift	Uncertain	0.026	D;D
Sift4G	Uncertain	0.024	D;D
Polyphen		0.29	B;B
Vest4		0.33
MutPred		0.52		Gain of stability (P = 0.0068);Gain of stability (P = 0.0068);
MVP		0.94
MPC		0.23
ClinPred		0.95	D
GERP RS		5.1
Varity_R		0.24
gMVP		0.85

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-99513848;