chr3-99795129-C-T
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate
The NM_020351.4(COL8A1):c.1228C>T(p.Pro410Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000166 in 1,613,720 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.00028 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00015 ( 0 hom. )
Consequence
COL8A1
NM_020351.4 missense
NM_020351.4 missense
Scores
1
11
6
Clinical Significance
Conservation
PhyloP100: 5.00
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.013157487).
BP6
?
Variant 3-99795129-C-T is Benign according to our data. Variant chr3-99795129-C-T is described in ClinVar as [Benign]. Clinvar id is 3055600.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL8A1 | NM_020351.4 | c.1228C>T | p.Pro410Ser | missense_variant | 4/4 | ENST00000652472.1 | |
COL8A1 | NM_001850.5 | c.1228C>T | p.Pro410Ser | missense_variant | 5/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL8A1 | ENST00000652472.1 | c.1228C>T | p.Pro410Ser | missense_variant | 4/4 | NM_020351.4 | P1 | ||
COL8A1 | ENST00000261037.7 | c.1228C>T | p.Pro410Ser | missense_variant | 5/5 | 1 | P1 | ||
COL8A1 | ENST00000273342.8 | c.1228C>T | p.Pro410Ser | missense_variant | 4/4 | 2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000276 AC: 42AN: 152024Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000659 AC: 165AN: 250258Hom.: 1 AF XY: 0.000628 AC XY: 85AN XY: 135384
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GnomAD4 exome AF: 0.000154 AC: 225AN: 1461578Hom.: 0 Cov.: 32 AF XY: 0.000138 AC XY: 100AN XY: 727120
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GnomAD4 genome ? AF: 0.000283 AC: 43AN: 152142Hom.: 0 Cov.: 32 AF XY: 0.000336 AC XY: 25AN XY: 74372
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
COL8A1-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Aug 09, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Uncertain
D;D
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
M_CAP
Uncertain
D
MetaRNN
Benign
T;T
MetaSVM
Uncertain
D
MutationAssessor
Benign
L;L
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D
REVEL
Uncertain
Sift
Uncertain
D;D
Sift4G
Benign
T;T
Polyphen
P;P
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at