6-31111487-C-T

Variant names:

• chr6-31111487-C-T
• rs2233984
• NM_014070.3:c.872G>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014070.3(C6orf15):​c.872G>A​(p.Gly291Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0779 in 1,611,930 control chromosomes in the GnomAD database, including 6,323 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.067 (501 hom., cov: 33)
  • Exomes 𝑓: 0.079 (5822 hom.)
• Consequence: C6orf15 NM_014070.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.284

Genes affected

C6orf15 (HGNC:13927): (chromosome 6 open reading frame 15) Predicted to enable several functions, including collagen V binding activity; fibronectin binding activity; and glycosaminoglycan binding activity. Predicted to be involved in extracellular matrix organization. Predicted to be located in interstitial matrix. Predicted to be active in extracellular matrix. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.003255248).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.202 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C6orf15	NM_014070.3	c.872G>A	p.Gly291Asp	missense_variant	Exon 2 of 2	ENST00000259870.4	NP_054789.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C6orf15	ENST00000259870.4	c.872G>A	p.Gly291Asp	missense_variant	Exon 2 of 2	1	NM_014070.3	ENSP00000259870.3

Frequencies

GnomAD3 genomes AF: 0.0667 AC: 10138 AN: 152004 Hom.: 505 Cov.: 33

Gnomad AFR AF: 0.0147

Gnomad AMI AF: 0.0318

Gnomad AMR AF: 0.0894

Gnomad ASJ AF: 0.0450

Gnomad EAS AF: 0.213

Gnomad SAS AF: 0.134

Gnomad FIN AF: 0.0880

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.0751

Gnomad OTH AF: 0.0751

GnomAD3 exomes AF: 0.100 AC: 24616 AN: 245610 Hom.: 1639 AF XY: 0.103 AC XY: 13764 AN XY: 133858

Gnomad AFR exome AF: 0.0127

Gnomad AMR exome AF: 0.125

Gnomad ASJ exome AF: 0.0354

Gnomad EAS exome AF: 0.216

Gnomad SAS exome AF: 0.153

Gnomad FIN exome AF: 0.0901

Gnomad NFE exome AF: 0.0788

Gnomad OTH exome AF: 0.0976

GnomAD4 exome AF: 0.0791 AC: 115512 AN: 1459808 Hom.: 5822 Cov.: 68 AF XY: 0.0821 AC XY: 59600 AN XY: 726114

Gnomad4 AFR exome AF: 0.0137

Gnomad4 AMR exome AF: 0.121

Gnomad4 ASJ exome AF: 0.0371

Gnomad4 EAS exome AF: 0.212

Gnomad4 SAS exome AF: 0.153

Gnomad4 FIN exome AF: 0.0897

Gnomad4 NFE exome AF: 0.0693

Gnomad4 OTH exome AF: 0.0742

GnomAD4 genome AF: 0.0665 AC: 10123 AN: 152122 Hom.: 501 Cov.: 33 AF XY: 0.0693 AC XY: 5152 AN XY: 74370

Gnomad4 AFR AF: 0.0147

Gnomad4 AMR AF: 0.0889

Gnomad4 ASJ AF: 0.0450

Gnomad4 EAS AF: 0.213

Gnomad4 SAS AF: 0.133

Gnomad4 FIN AF: 0.0880

Gnomad4 NFE AF: 0.0751

Gnomad4 OTH AF: 0.0748

Alfa AF: 0.0790 Hom.: 1289

Bravo AF: 0.0634

TwinsUK AF: 0.0601 AC: 223

ALSPAC AF: 0.0615 AC: 237

ESP6500AA AF: 0.0152 AC: 54

ESP6500EA AF: 0.0655 AC: 463

ExAC AF: 0.0998 AC: 11723

Asia WGS AF: 0.134 AC: 466 AN: 3476

EpiCase AF: 0.0854

EpiControl AF: 0.0845

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.71	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	18
DANN	Benign	0.97
DEOGEN2	Benign	0.050	T
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.61
FATHMM_MKL	Benign	0.15	N
MetaRNN	Benign	0.0033	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.90	L
PROVEAN	Pathogenic	-4.8	D
REVEL	Benign	0.047
Sift	Benign	0.12	T
Sift4G	Uncertain	0.014	D
Polyphen		1.0	D
Vest4		0.23
MPC		1.0
ClinPred		0.084	T
GERP RS		0.066
Varity_R		0.048
gMVP		0.36

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

LitVar

Other links and lift over

dbSNP: rs2233984; hg19: chr6-31079264; COSMIC: COSV52538262; COSMIC: COSV52538262;