NM_014070.3:c.493A>G

Variant names:

• chr6-31111866-T-C
• rs1265054
• NM_014070.3:c.493A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014070.3(C6orf15):​c.493A>G​(p.Lys165Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.527 in 1,612,024 control chromosomes in the GnomAD database, including 225,985 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.53 (21249 hom., cov: 33)
  • Exomes 𝑓: 0.53 (204736 hom.)
• Consequence: C6orf15 NM_014070.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0750
• Publications: 28 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.6201651E-5).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.572 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C6orf15	NM_014070.3	c.493A>G	p.Lys165Glu	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.493A>G	p.Lys165Glu	missense_variant	Exon 2 of 2	1	NM_014070.3	ENSP00000259870.3

Frequencies

GnomAD3 genomes AF: 0.529 AC: 80409 AN: 151946 Hom.: 21233 Cov.: 33

Gnomad AFR AF: 0.548

Gnomad AMI AF: 0.525

Gnomad AMR AF: 0.523

Gnomad ASJ AF: 0.696

Gnomad EAS AF: 0.473

Gnomad SAS AF: 0.589

Gnomad FIN AF: 0.507

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.513

Gnomad OTH AF: 0.565

GnomAD2 exomes AF: 0.537 AC: 131838 AN: 245518 AF XY: 0.545

Gnomad AFR exome AF: 0.552

Gnomad AMR exome AF: 0.517

Gnomad ASJ exome AF: 0.692

Gnomad EAS exome AF: 0.480

Gnomad FIN exome AF: 0.495

Gnomad NFE exome AF: 0.519

Gnomad OTH exome AF: 0.535

GnomAD4 exome AF: 0.526 AC: 768362 AN: 1459960 Hom.: 204736 Cov.: 56 AF XY: 0.531 AC XY: 385657 AN XY: 726166

African (AFR) AF: 0.569 AC: 19060 AN: 33468

American (AMR) AF: 0.523 AC: 23383 AN: 44672

Ashkenazi Jewish (ASJ) AF: 0.682 AC: 17794 AN: 26106

East Asian (EAS) AF: 0.467 AC: 18536 AN: 39682

South Asian (SAS) AF: 0.629 AC: 54273 AN: 86236

European-Finnish (FIN) AF: 0.496 AC: 25911 AN: 52278

Middle Eastern (MID) AF: 0.614 AC: 3541 AN: 5764

European-Non Finnish (NFE) AF: 0.516 AC: 573155 AN: 1111404

Other (OTH) AF: 0.542 AC: 32709 AN: 60350

GnomAD4 genome AF: 0.529 AC: 80462 AN: 152064 Hom.: 21249 Cov.: 33 AF XY: 0.527 AC XY: 39177 AN XY: 74342

African (AFR) AF: 0.548 AC: 22711 AN: 41466

American (AMR) AF: 0.522 AC: 7991 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.696 AC: 2418 AN: 3472

East Asian (EAS) AF: 0.474 AC: 2440 AN: 5152

South Asian (SAS) AF: 0.590 AC: 2850 AN: 4830

European-Finnish (FIN) AF: 0.507 AC: 5376 AN: 10600

Middle Eastern (MID) AF: 0.602 AC: 177 AN: 294

European-Non Finnish (NFE) AF: 0.513 AC: 34836 AN: 67928

Other (OTH) AF: 0.562 AC: 1185 AN: 2110

Alfa AF: 0.527 Hom.: 44429

Bravo AF: 0.529

TwinsUK AF: 0.505 AC: 1871

ALSPAC AF: 0.513 AC: 1979

ESP6500AA AF: 0.577 AC: 2085

ESP6500EA AF: 0.555 AC: 3923

ExAC AF: 0.534 AC: 62863

Asia WGS AF: 0.526 AC: 1833 AN: 3478

EpiCase AF: 0.541

EpiControl AF: 0.551

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.049
BayesDel_addAF	Benign	-0.87	T
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.57
DANN	Benign	0.30
DEOGEN2	Benign	0.0013	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.00023	N
MetaRNN	Benign	0.000016	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	-0.83	N
PhyloP100		-0.075
PROVEAN	Benign	2.5	N
REVEL	Benign	0.040
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.011
MPC		0.35
ClinPred		0.0020	T
GERP RS		2.5
Varity_R		0.057
gMVP		0.054
Mutation Taster		=100/0	polymorphism (auto)

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: rs1265054; hg19: chr6-31079643; COSMIC: COSV52538485; COSMIC: COSV52538485;