chr3-130376506-G-A
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Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_001278298.2(COL6A5):c.337G>A(p.Ala113Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000112 in 1,605,314 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00012 ( 0 hom. )
Consequence
COL6A5
NM_001278298.2 missense
NM_001278298.2 missense
Scores
6
8
4
Clinical Significance
Conservation
PhyloP100: 7.40
Genes affected
COL6A5 (HGNC:26674): (collagen type VI alpha 5 chain) This gene encodes a member of the collagen superfamily of proteins. The encoded protein contains multiple von Willebrand factor A-like domains and may interact with the alpha 1 and alpha 2 chains of collagen VI to form the complete collagen VI trimer. Polymorphisms in this gene may be linked to dermal phenotypes, such as eczema. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2013]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.977
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
COL6A5 | NM_001278298.2 | c.337G>A | p.Ala113Thr | missense_variant | 3/41 | ENST00000373157.9 | NP_001265227.1 | |
COL6A5 | NM_153264.7 | c.337G>A | p.Ala113Thr | missense_variant | 3/40 | NP_694996.5 | ||
COL6A5 | NR_022012.3 | n.675G>A | non_coding_transcript_exon_variant | 3/42 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
COL6A5 | ENST00000373157.9 | c.337G>A | p.Ala113Thr | missense_variant | 3/41 | 2 | NM_001278298.2 | ENSP00000362250.5 | ||
COL6A5 | ENST00000312481.11 | n.337G>A | non_coding_transcript_exon_variant | 3/42 | 1 | ENSP00000309762.7 | ||||
COL6A5 | ENST00000512836.6 | c.337G>A | p.Ala113Thr | missense_variant | 3/40 | 2 | ENSP00000422898.2 |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152096Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000301 AC: 7AN: 232498Hom.: 0 AF XY: 0.0000397 AC XY: 5AN XY: 126036
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GnomAD4 exome AF: 0.000120 AC: 175AN: 1453218Hom.: 0 Cov.: 32 AF XY: 0.000109 AC XY: 79AN XY: 722140
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GnomAD4 genome AF: 0.0000329 AC: 5AN: 152096Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74276
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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 | Jul 27, 2024 | The c.337G>A (p.A113T) alteration is located in exon 3 (coding exon 2) of the COL6A5 gene. This alteration results from a G to A substitution at nucleotide position 337, causing the alanine (A) at amino acid position 113 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Uncertain
D
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T
M_CAP
Benign
D
MetaRNN
Pathogenic
D
MetaSVM
Pathogenic
D
PrimateAI
Benign
T
PROVEAN
Uncertain
D
REVEL
Pathogenic
Sift
Pathogenic
D
Sift4G
Pathogenic
D
Vest4
MutPred
Gain of disorder (P = 0.1775);
MVP
MPC
ClinPred
D
GERP RS
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