rs2233984

chr6-31111487-C-Achr6-31111487-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_014070.3(C6orf15):c.872G>T(p.Gly291Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,846 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G291D) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C6orf15	NM_014070.3	c.872G>T	p.Gly291Val	missense_variant	2/2	ENST00000259870.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C6orf15	ENST00000259870.4	c.872G>T	p.Gly291Val	missense_variant	2/2	1	NM_014070.3	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459846 Hom.: 0 Cov.: 68 AF XY: 0.00000138 AC XY: 1 AN XY: 726140

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ExAC AF: 0.00000851 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
Cadd	Benign	18
Dann	Benign	0.97
DEOGEN2	Benign	0.053	T
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.78
FATHMM_MKL	Benign	0.082	N
M_CAP	Benign	0.013	T
MetaRNN	Uncertain	0.52	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	L
MutationTaster	Benign	0.15	P
PROVEAN	Pathogenic	-6.0	D
REVEL	Benign	0.083
Sift	Uncertain	0.013	D
Sift4G	Uncertain	0.0070	D
Polyphen		0.93	P
Vest4		0.31
MutPred		0.38		Gain of sheet (P = 0.0061);
MVP		0.40
MPC		1.0
ClinPred		0.83	D
GERP RS		0.066
Varity_R		0.038
gMVP		0.49

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: COSV52539561; COSMIC: COSV52539561;