dbSNP rs200271005: C6orf132:p.His873Gln (chr6-42105293-G-C) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -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. 15/21 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

Publications

2 publications found

Variant links:

Genes affected

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

C6orf132 Gene-Disease associations (from GenCC):

schizophrenia
Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

C6orf132 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

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

BS2

High Homozygotes in GnomAdExome4 at 7 Unknown gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001164446.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C6orf132	NM_001164446.3	MANE Select	c.2619C>G	p.His873Gln	missense	Exon 4 of 5	NP_001157918.1	Q5T0Z8-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
C6orf132	ENST00000341865.9	TSL:5 MANE Select	c.2619C>G	p.His873Gln	missense	Exon 4 of 5	ENSP00000341368.4	Q5T0Z8-1
C6orf132	ENST00000696229.1		n.*3231C>G		non_coding_transcript_exon	Exon 5 of 6	ENSP00000512495.1	Q5T0Z8-2
C6orf132	ENST00000696229.1		n.*3231C>G		3_prime_UTR	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

GnomAD2 exomes

AF:

0.00109

AC:

154

AN:

141892

AF XY:

0.00109

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 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

African (AFR)

AF:

0.000317

AC:

AN:

31594

American (AMR)

AF:

0.000532

AC:

AN:

35700

Ashkenazi Jewish (ASJ)

AF:

0.00723

AC:

182

AN:

25182

East Asian (EAS)

AF:

0.00

AC:

AN:

35734

South Asian (SAS)

AF:

0.000164

AC:

AN:

79236

European-Finnish (FIN)

AF:

0.0000860

AC:

AN:

34904

Middle Eastern (MID)

AF:

0.000176

AC:

AN:

5696

European-Non Finnish (NFE)

AF:

0.00198

AC:

2133

AN:

1078882

Other (OTH)

AF:

0.00164

AC:

AN:

57916

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

180

359

539

718

898

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

180

270

360

450

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000854

AC:

130

AN:

152192

Hom.:

Cov.:

AF XY:

0.000874

AC XY:

AN XY:

74362

show subpopulations

African (AFR)

AF:

0.000289

AC:

AN:

41456

American (AMR)

AF:

0.000720

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00547

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.0000942

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00125

AC:

AN:

68020

Other (OTH)

AF:

0.000957

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.74

CADD

Benign

3.9

(source)

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

PhyloP100

0.20

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

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over