3-130471872-G-T

Variant names:

• chr3-130471872-G-T
• rs73868680
• NM_001278298.2:c.7765G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001278298.2(COL6A5):​c.7765G>T​(p.Ala2589Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A2589T) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: COL6A5 NM_001278298.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.413
• Publications: 7 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09063086).

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.7765G>T	p.Ala2589Ser	missense	Exon 40 of 41	NP_001265227.1	H0Y393
	COL6A5	NM_153264.7		c.7574+905G>T		intron	N/A	NP_694996.5
	COL6A5	NR_022012.3		n.8103G>T		non_coding_transcript_exon	Exon 40 of 42

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL6A5	ENST00000373157.9	TSL:2 MANE Select	c.7765G>T	p.Ala2589Ser	missense	Exon 40 of 41	ENSP00000362250.5	H0Y393
	COL6A5	ENST00000312481.11	TSL:1	n.7765G>T		non_coding_transcript_exon	Exon 40 of 42	ENSP00000309762.7	A8TX70-1
	COL6A5	ENST00000512482.1	TSL:5	c.1270G>T	p.Ala424Ser	missense	Exon 5 of 6	ENSP00000424968.1	H0Y9T2

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD2 exomes AF: 0.0000139 AC: 1 AN: 72030 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000652

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 Data not reliable, filtered out with message: AS_VQSR AF: 7.23e-7 AC: 1 AN: 1382822 Hom.: 0 Cov.: 41 AF XY: 0.00 AC XY: 0 AN XY: 682390

African (AFR) AF: 0.00 AC: 0 AN: 31534

American (AMR) AF: 0.0000280 AC: 1 AN: 35686

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25150

East Asian (EAS) AF: 0.00 AC: 0 AN: 35700

South Asian (SAS) AF: 0.00 AC: 0 AN: 79200

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33884

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5682

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1078136

Other (OTH) AF: 0.00 AC: 0 AN: 57850

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	7.6
DANN	Uncertain	0.98
DEOGEN2	Benign	0.012	T
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.78
FATHMM_MKL	Benign	0.057	N
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.080	D
MetaRNN	Benign	0.091	T
MetaSVM	Benign	-0.57	T
PhyloP100		0.41
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.41	N
REVEL	Benign	0.10
Sift	Benign	0.34	T
Sift4G	Benign	0.068	T
Vest4		0.099
MVP		0.31
MPC		0.033
ClinPred		0.064	T
GERP RS		1.2
gMVP		0.026
Mutation Taster		=82/18	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: rs73868680; hg19: chr3-130190716;