Variant chr6-165301975-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_144980.4(C6orf118):c.347C>T(p.Thr116Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00131 in 1,613,586 control chromosomes in the GnomAD database, including 2 homozygotes. 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 0.00064 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0014 ( 2 hom. )

Consequence

C6orf118
NM_144980.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.689

Variant links:

Genes affected

C6orf118 (HGNC:21233): (chromosome 6 open reading frame 118)

C6orf118 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.07698861).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C6orf118	NM_144980.4 link	c.347C>T	p.Thr116Met	missense_variant	2/9	ENST00000230301.9	NP_659417.2	Q5T5N4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C6orf118	ENST00000230301.9 link	c.347C>T	p.Thr116Met	missense_variant	2/9	1	NM_144980.4	ENSP00000230301.8		Q5T5N4

Frequencies

GnomAD3 genomes

AF:

0.000644

AC:

AN:

152140

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000290

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00122

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000522

AC:

131

AN:

250862

Hom.:

AF XY:

0.000457

AC XY:

AN XY:

135618

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000141

Gnomad NFE exome

AF:

0.00105

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.00138

AC:

2011

AN:

1461446

Hom.:

Cov.:

AF XY:

0.00126

AC XY:

918

AN XY:

727014

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

Gnomad4 AMR exome

AF:

0.000201

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000170

Gnomad4 NFE exome

AF:

0.00174

Gnomad4 OTH exome

AF:

0.000845

GnomAD4 genome

AF:

0.000644

AC:

AN:

152140

Hom.:

Cov.:

AF XY:

0.000552

AC XY:

AN XY:

74304

show subpopulations

Gnomad4 AFR

AF:

0.000290

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.00122

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.00112

Hom.:

Bravo

AF:

0.000620

TwinsUK

AF:

0.00162

AC:

ALSPAC

AF:

0.00234

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000930

AC:

ExAC

AF:

0.000461

AC:

EpiCase

AF:

0.00125

EpiControl

AF:

0.00101

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

Sep 16, 2021

The c.347C>T (p.T116M) alteration is located in exon 2 (coding exon 2) of the C6orf118 gene. This alteration results from a C to T substitution at nucleotide position 347, causing the threonine (T) at amino acid position 116 to be replaced by a methionine (M). 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

0.21

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.073

Eigen

Benign

-0.17

Eigen_PC

Benign

-0.26

FATHMM_MKL

Benign

0.44

LIST_S2

Benign

0.71

M_CAP

Benign

0.015

MetaRNN

Benign

0.077

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.0

PROVEAN

Pathogenic

-5.3

REVEL

Benign

0.23

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.041

Polyphen

0.99

Vest4

0.26

MVP

0.099

MPC

0.34

ClinPred

0.14

GERP RS

4.5

Varity_R

0.27

gMVP

0.53

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