Genetic Variant C6orf132:p.His873Gln (chr6-42105293-G-C) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001164446.3(C6orf132):c.2619C>G(p.His873Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00168 in 1,537,036 control chromosomes in the GnomAD database, including 7 homozygotes. 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 0.00085 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0018 ( 7 hom. )

Consequence

C6orf132
NM_001164446.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.204

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0038240254).

BS2

High Homozygotes in GnomAdExome4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C6orf132	NM_001164446.3 link	c.2619C>G	p.His873Gln	missense_variant	Exon 4 of 5	ENST00000341865.9	NP_001157918.1	Q5T0Z8-1
C6orf132	XM_047419258.1 link	c.2064C>G	p.His688Gln	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.2619C>G	p.His873Gln	missense_variant	Exon 4 of 5	5	NM_001164446.3	ENSP00000341368.4	Q5T0Z8-1
C6orf132	ENST00000696229.1 link	n.*3231C>G		non_coding_transcript_exon_variant	Exon 5 of 6			ENSP00000512495.1	Q5T0Z8-2
C6orf132	ENST00000696229.1 link	n.*3231C>G		3_prime_UTR_variant	Exon 5 of 6			ENSP00000512495.1	Q5T0Z8-2

Frequencies

GnomAD3 genomes

AF:

0.000854

AC:

130

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000289

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000720

Gnomad ASJ

AF:

0.00547

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00125

Gnomad OTH

AF:

0.000957

GnomAD3 exomes

AF:

0.00109

AC:

154

AN:

141892

Hom.:

AF XY:

0.00109

AC XY:

AN XY:

75858

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000488

Gnomad ASJ exome

AF:

0.00666

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000132

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00139

Gnomad OTH exome

AF:

0.000473

GnomAD4 exome

AF:

0.00177

AC:

2456

AN:

1384844

Hom.:

Cov.:

AF XY:

0.00173

AC XY:

1179

AN XY:

683354

show subpopulations

Gnomad4 AFR exome

AF:

0.000317

Gnomad4 AMR exome

AF:

0.000532

Gnomad4 ASJ exome

AF:

0.00723

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000164

Gnomad4 FIN exome

AF:

0.0000860

Gnomad4 NFE exome

AF:

0.00198

Gnomad4 OTH exome

AF:

0.00164

GnomAD4 genome

AF:

0.000854

AC:

130

AN:

152192

Hom.:

Cov.:

AF XY:

0.000874

AC XY:

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.000289

Gnomad4 AMR

AF:

0.000720

Gnomad4 ASJ

AF:

0.00547

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.00125

Gnomad4 OTH

AF:

0.000957

Alfa

AF:

0.00169

Hom.:

Bravo

AF:

0.00104

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.00208

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00157

AC:

ExAC

AF:

0.000801

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 03, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2619C>G (p.H873Q) alteration is located in exon 4 (coding exon 4) of the C6orf132 gene. This alteration results from a C to G substitution at nucleotide position 2619, causing the histidine (H) at amino acid position 873 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

0.093

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.74

CADD

Benign

3.9

DANN

Benign

0.69

DEOGEN2

Benign

0.0057

Eigen

Benign

-0.89

Eigen_PC

Benign

-0.99

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.19

M_CAP

Benign

0.013

MetaRNN

Benign

0.0038

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.0

PROVEAN

Benign

-1.3

REVEL

Benign

0.033

Sift

Benign

0.34

Sift4G

Benign

0.38

Vest4

0.016

MutPred

0.070

Gain of helix (P = 0.0325);

MVP

0.014

ClinPred

0.0063

GERP RS

-0.11

Varity_R

0.045

gMVP

0.055

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