chr3-130376350-C-A

Variant summary

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

The NM_001278298.2(COL6A5):​c.181C>A​(p.Pro61Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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

COL6A5
NM_001278298.2 missense

Scores

2
6
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.985
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 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
COL6A5NM_001278298.2 linkc.181C>A p.Pro61Thr missense_variant 3/41 ENST00000373157.9 NP_001265227.1 A8TX70H0Y393
COL6A5NM_153264.7 linkc.181C>A p.Pro61Thr missense_variant 3/40 NP_694996.5 A8TX70-2
COL6A5NR_022012.3 linkn.519C>A non_coding_transcript_exon_variant 3/42

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
COL6A5ENST00000373157.9 linkc.181C>A p.Pro61Thr missense_variant 3/412 NM_001278298.2 ENSP00000362250.5 H0Y393
COL6A5ENST00000312481.11 linkn.181C>A non_coding_transcript_exon_variant 3/421 ENSP00000309762.7 A8TX70-1
COL6A5ENST00000512836.6 linkc.181C>A p.Pro61Thr missense_variant 3/402 ENSP00000422898.2 A8TX70-2H0Y935

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
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsDec 03, 2024The c.181C>A (p.P61T) alteration is located in exon 3 (coding exon 2) of the COL6A5 gene. This alteration results from a C to A substitution at nucleotide position 181, causing the proline (P) at amino acid position 61 to be replaced by a threonine (T). 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
0.22
BayesDel_addAF
Uncertain
0.021
T
BayesDel_noAF
Benign
-0.21
CADD
Benign
22
DANN
Uncertain
0.99
DEOGEN2
Benign
0.19
T
Eigen
Benign
0.070
Eigen_PC
Benign
-0.043
FATHMM_MKL
Benign
0.14
N
LIST_S2
Uncertain
0.90
D
M_CAP
Benign
0.037
D
MetaRNN
Uncertain
0.44
T
MetaSVM
Benign
-0.51
T
PrimateAI
Benign
0.36
T
PROVEAN
Pathogenic
-4.7
D
REVEL
Uncertain
0.35
Sift
Uncertain
0.022
D
Sift4G
Pathogenic
0.0
D
Vest4
0.39
MutPred
0.46
Gain of MoRF binding (P = 0.0911);
MVP
0.49
MPC
0.13
ClinPred
0.85
D
GERP RS
4.3
gMVP
0.37

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-130095193; API