3-130376506-G-C

Variant names:

• chr3-130376506-G-C
• NM_001278298.2:c.337G>C

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_001278298.2(COL6A5):​c.337G>C​(p.Ala113Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,453,218 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: COL6A5 NM_001278298.2 missense
• Clinical Significance: Not reported in ClinVar
• 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]

ACMG classification

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, 0.983

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL6A5	NM_001278298.2	c.337G>C	p.Ala113Pro	missense_variant	Exon 3 of 41	ENST00000373157.9	NP_001265227.1
COL6A5	NM_153264.7	c.337G>C	p.Ala113Pro	missense_variant	Exon 3 of 40		NP_694996.5
COL6A5	NR_022012.3	n.675G>C		non_coding_transcript_exon_variant	Exon 3 of 42

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL6A5	ENST00000373157.9	c.337G>C	p.Ala113Pro	missense_variant	Exon 3 of 41	2	NM_001278298.2	ENSP00000362250.5
COL6A5	ENST00000312481.11	n.337G>C		non_coding_transcript_exon_variant	Exon 3 of 42	1		ENSP00000309762.7
COL6A5	ENST00000512836.6	c.337G>C	p.Ala113Pro	missense_variant	Exon 3 of 40	2		ENSP00000422898.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.88e-7 AC: 1 AN: 1453218 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 722140

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 9.03e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.92
BayesDel_addAF	Pathogenic	0.30	D
BayesDel_noAF	Pathogenic	0.19
CADD	Uncertain	25
DANN	Benign	0.97
DEOGEN2	Uncertain	0.51	D
Eigen	Uncertain	0.68
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.046	D
MetaRNN	Pathogenic	0.98	D
MetaSVM	Pathogenic	0.97	D
PrimateAI	Benign	0.45	T
PROVEAN	Pathogenic	-4.5	D
REVEL	Pathogenic	0.81
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Vest4		0.75
MutPred		0.88		Gain of disorder (P = 0.0715);
MVP		0.74
MPC		0.26
ClinPred		0.99	D
GERP RS		5.1
gMVP		0.87

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: chr3-130095349;