Genetic Variant C6orf132:p.Arg337Gln (chr6-42106902-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001164446.3(C6orf132):c.1010G>A(p.Arg337Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000208 in 1,534,816 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 26)

Exomes 𝑓: 0.000020 ( 0 hom. )

Consequence

C6orf132
NM_001164446.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0510

Variant links:

Genes affected

C6orf132 (HGNC:21288): (chromosome 6 open reading frame 132)

C6orf132 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.060685307).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C6orf132	NM_001164446.3 link	c.1010G>A	p.Arg337Gln	missense_variant	Exon 4 of 5	ENST00000341865.9	NP_001157918.1	Q5T0Z8-1
C6orf132	XM_047419258.1 link	c.455G>A	p.Arg152Gln	missense_variant	Exon 3 of 4		XP_047275214.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
C6orf132	ENST00000341865.9 link	c.1010G>A	p.Arg337Gln	missense_variant	Exon 4 of 5	5	NM_001164446.3	ENSP00000341368.4	Q5T0Z8-1
C6orf132	ENST00000696229.1 link	n.*1622G>A		non_coding_transcript_exon_variant	Exon 5 of 6			ENSP00000512495.1	Q5T0Z8-2
C6orf132	ENST00000696229.1 link	n.*1622G>A		3_prime_UTR_variant	Exon 5 of 6			ENSP00000512495.1	Q5T0Z8-2

Frequencies

GnomAD3 genomes

AF:

0.0000265

AC:

AN:

150992

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000488

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:

0.0000295

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000216

AC:

AN:

139178

Hom.:

AF XY:

0.0000268

AC XY:

AN XY:

74652

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000882

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000179

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000202

AC:

AN:

1383824

Hom.:

Cov.:

AF XY:

0.0000234

AC XY:

AN XY:

682678

show subpopulations

Gnomad4 AFR exome

AF:

0.0000317

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000505

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000204

Gnomad4 OTH exome

AF:

0.0000173

GnomAD4 genome

AF:

0.0000265

AC:

AN:

150992

Hom.:

Cov.:

AF XY:

0.0000136

AC XY:

AN XY:

73698

show subpopulations

Gnomad4 AFR

AF:

0.0000488

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:

0.0000295

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 09, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1010G>A (p.R337Q) alteration is located in exon 4 (coding exon 4) of the C6orf132 gene. This alteration results from a G to A substitution at nucleotide position 1010, causing the arginine (R) at amino acid position 337 to be replaced by a glutamine (Q). 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

0.10

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.011

Eigen

Benign

-0.72

Eigen_PC

Benign

-0.76

FATHMM_MKL

Benign

0.36

LIST_S2

Benign

0.48

M_CAP

Benign

0.029

MetaRNN

Benign

0.061

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.69

PROVEAN

Benign

-1.5

REVEL

Benign

0.012

Sift

Uncertain

0.022

Sift4G

Benign

0.45

Vest4

0.097

MVP

0.048

ClinPred

0.21

GERP RS

0.95

Varity_R

0.15

gMVP

0.11

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