chr3-130373645-A-G

Variant names:

• chr3-130373645-A-G
• NM_001278298.2:c.7A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001278298.2(COL6A5):​c.7A>G​(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. 16/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: COL6A5 NM_001278298.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.15
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001278298.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL6A5	NM_001278298.2	MANE Select	c.7A>G	p.Ile3Val	missense	Exon 2 of 41	NP_001265227.1	H0Y393
	COL6A5	NM_153264.7		c.7A>G	p.Ile3Val	missense	Exon 2 of 40	NP_694996.5
	COL6A5	NR_022012.3		n.345A>G		non_coding_transcript_exon	Exon 2 of 42

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL6A5	ENST00000373157.9	TSL:2 MANE Select	c.7A>G	p.Ile3Val	missense	Exon 2 of 41	ENSP00000362250.5	H0Y393
	COL6A5	ENST00000312481.11	TSL:1	n.7A>G		non_coding_transcript_exon	Exon 2 of 42	ENSP00000309762.7	A8TX70-1
	COL6A5	ENST00000512836.6	TSL:2	c.7A>G	p.Ile3Val	missense	Exon 2 of 40	ENSP00000422898.2	A8TX70-2

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

African (AFR) AF: 0.00 AC: 0 AN: 31152

American (AMR) AF: 0.0000286 AC: 1 AN: 35008

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24986

East Asian (EAS) AF: 0.00 AC: 0 AN: 35500

South Asian (SAS) AF: 0.00 AC: 0 AN: 76306

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49142

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5546

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1065506

Other (OTH) AF: 0.0000174 AC: 1 AN: 57362

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		3.1
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
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

hg19: chr3-130092488;