Variant 6-31111530-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014070.3(C6orf15):c.829C>T(p.Arg277Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000355 in 1,607,828 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000036 ( 0 hom. )

Consequence

C6orf15
NM_014070.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.631

Variant links:

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]

C6orf15 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06878194).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C6orf15	NM_014070.3 linkuse as main transcript	c.829C>T	p.Arg277Trp	missense_variant	2/2	ENST00000259870.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C6orf15	ENST00000259870.4 linkuse as main transcript	c.829C>T	p.Arg277Trp	missense_variant	2/2	1	NM_014070.3	P1

Frequencies

GnomAD3 genomes

AF:

0.0000264

AC:

AN:

151472

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000443

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000406

AC:

AN:

246364

Hom.:

AF XY:

0.0000149

AC XY:

AN XY:

134332

show subpopulations

Gnomad AFR exome

AF:

0.0000668

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000100

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000723

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000357

AC:

AN:

1456238

Hom.:

Cov.:

AF XY:

0.0000359

AC XY:

AN XY:

724410

show subpopulations

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:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000442

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000330

AC:

AN:

151590

Hom.:

Cov.:

AF XY:

0.0000405

AC XY:

AN XY:

74122

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000443

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000116

Hom.:

Bravo

AF:

0.0000340

ESP6500AA

AF:

0.000287

AC:

ESP6500EA

AF:

0.000146

AC:

ExAC

AF:

0.0000425

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000237

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 26, 2021

The c.829C>T (p.R277W) alteration is located in exon 2 (coding exon 2) of the C6orf15 gene. This alteration results from a C to T substitution at nucleotide position 829, causing the arginine (R) at amino acid position 277 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.59

Cadd

Benign

Dann

Uncertain

0.99

DEOGEN2

Benign

0.021

Eigen

Benign

-0.82

Eigen_PC

Benign

-0.93

FATHMM_MKL

Benign

0.021

M_CAP

Benign

0.010

MetaRNN

Benign

0.069

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.60

MutationTaster

Benign

1.0

PROVEAN

Uncertain

-3.6

REVEL

Benign

0.037

Sift

Benign

0.11

Sift4G

Uncertain

0.0030

Polyphen

0.24

Vest4

0.19

MVP

0.44

MPC

0.88

ClinPred

0.097

GERP RS

-1.3

Varity_R

0.075

gMVP

0.42

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over