chr3-130376350-C-A

Position:

• 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.985

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]

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
COL6A5	NM_001278298.2	c.181C>A	p.Pro61Thr	missense_variant	3/41	ENST00000373157.9	NP_001265227.1
COL6A5	NM_153264.7	c.181C>A	p.Pro61Thr	missense_variant	3/40		NP_694996.5
COL6A5	NR_022012.3	n.519C>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.181C>A	p.Pro61Thr	missense_variant	3/41	2	NM_001278298.2	ENSP00000362250.5
COL6A5	ENST00000312481.11	n.181C>A		non_coding_transcript_exon_variant	3/42	1		ENSP00000309762.7
COL6A5	ENST00000512836.6	c.181C>A	p.Pro61Thr	missense_variant	3/40	2		ENSP00000422898.2

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

Dec 03, 2024

The 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;