3-130376666-C-T

Variant names:

• chr3-130376666-C-T
• rs528892434
• NM_001278298.2:c.497C>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_001278298.2(COL6A5):​c.497C>T​(p.Ser166Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000248 in 1,613,426 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000027 (0 hom.)
• Consequence: COL6A5 NM_001278298.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.17
• Publications: 1 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 -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.40010953).

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.497C>T	p.Ser166Phe	missense	Exon 3 of 41	NP_001265227.1	H0Y393
	COL6A5	NM_153264.7		c.497C>T	p.Ser166Phe	missense	Exon 3 of 40	NP_694996.5
	COL6A5	NR_022012.3		n.835C>T		non_coding_transcript_exon	Exon 3 of 42

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL6A5	ENST00000373157.9	TSL:2 MANE Select	c.497C>T	p.Ser166Phe	missense	Exon 3 of 41	ENSP00000362250.5	H0Y393
	COL6A5	ENST00000312481.11	TSL:1	n.497C>T		non_coding_transcript_exon	Exon 3 of 42	ENSP00000309762.7	A8TX70-1
	COL6A5	ENST00000512836.6	TSL:2	c.497C>T	p.Ser166Phe	missense	Exon 3 of 40	ENSP00000422898.2	A8TX70-2

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152100 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000656

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000141 AC: 35 AN: 247636 AF XY: 0.000111

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00102

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000267 AC: 39 AN: 1461208 Hom.: 0 Cov.: 32 AF XY: 0.0000206 AC XY: 15 AN XY: 726840

African (AFR) AF: 0.00 AC: 0 AN: 33456

American (AMR) AF: 0.000873 AC: 39 AN: 44660

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

East Asian (EAS) AF: 0.00 AC: 0 AN: 39676

South Asian (SAS) AF: 0.00 AC: 0 AN: 86212

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53352

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111614

Other (OTH) AF: 0.00 AC: 0 AN: 60350

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152218 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74430

African (AFR) AF: 0.00 AC: 0 AN: 41558

American (AMR) AF: 0.0000655 AC: 1 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68004

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000340

ExAC AF: 0.000182 AC: 22

ClinVar

ClinVar submissions as Germline

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	Pathogenic	0.88
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.16
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Benign	0.41	T
Eigen	Benign	0.12
Eigen_PC	Benign	-0.083
FATHMM_MKL	Benign	0.65	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.066	D
MetaRNN	Benign	0.40	T
MetaSVM	Uncertain	-0.087	T
PhyloP100		2.2
PrimateAI	Benign	0.44	T
PROVEAN	Uncertain	-4.3	D
REVEL	Uncertain	0.42
Sift	Uncertain	0.0030	D
Sift4G	Pathogenic	0.0	D
Vest4		0.71
MutPred		0.66		Loss of disorder (P = 0.0218)
MVP		0.65
MPC		0.24
ClinPred		0.70	D
GERP RS		3.4
gMVP		0.63
Mutation Taster		=84/16	polymorphism

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

Other links and lift over

dbSNP: rs528892434; hg19: chr3-130095509; COSMIC: COSV99594029;