chr3-130373645-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001278298.2(COL6A5):ā€‹c.7A>Gā€‹(p.Ile3Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000145 in 1,380,508 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0000014 ( 0 hom. )

Consequence

COL6A5
NM_001278298.2 missense

Scores

1
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.15
Variant links:
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_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.054009646).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
COL6A5NM_001278298.2 linkc.7A>G p.Ile3Val missense_variant 2/41 ENST00000373157.9 NP_001265227.1 A8TX70H0Y393
COL6A5NM_153264.7 linkc.7A>G p.Ile3Val missense_variant 2/40 NP_694996.5 A8TX70-2
COL6A5NR_022012.3 linkn.345A>G non_coding_transcript_exon_variant 2/42

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
COL6A5ENST00000373157.9 linkc.7A>G p.Ile3Val missense_variant 2/412 NM_001278298.2 ENSP00000362250.5 H0Y393
COL6A5ENST00000312481.11 linkn.7A>G non_coding_transcript_exon_variant 2/421 ENSP00000309762.7 A8TX70-1
COL6A5ENST00000512836.6 linkc.7A>G p.Ile3Val missense_variant 2/402 ENSP00000422898.2 A8TX70-2H0Y935

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000145
AC:
2
AN:
1380508
Hom.:
0
Cov.:
26
AF XY:
0.00
AC XY:
0
AN XY:
681050
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000286
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:
0.0000174
GnomAD4 genome
Cov.:
32

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 submitterclinical testingAmbry GeneticsNov 24, 2024The c.7A>G (p.I3V) alteration is located in exon 2 (coding exon 1) of the COL6A5 gene. This alteration results from a A to G substitution at nucleotide position 7, causing the isoleucine (I) at amino acid position 3 to be replaced by a valine (V). 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
0.11
BayesDel_addAF
Benign
-0.14
T
BayesDel_noAF
Benign
-0.44
CADD
Benign
19
DANN
Benign
0.64
DEOGEN2
Benign
0.0094
T
Eigen
Benign
-0.76
Eigen_PC
Benign
-0.70
FATHMM_MKL
Benign
0.68
D
LIST_S2
Benign
0.29
T
M_CAP
Benign
0.018
T
MetaRNN
Benign
0.054
T
MetaSVM
Benign
-0.62
T
PrimateAI
Benign
0.38
T
PROVEAN
Benign
-0.25
N
REVEL
Benign
0.13
Sift
Benign
0.19
T
Sift4G
Uncertain
0.021
D
Vest4
0.083
MutPred
0.23
Gain of sheet (P = 0.0221);
MVP
0.13
MPC
0.029
ClinPred
0.098
T
GERP RS
1.8
gMVP
0.20

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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: chr3-130092488; API