Genetic Variant NM_001164446.3:c.725C>T (chr6-42107187-G-A) – 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.725C>T(p.Pro242Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00137 in 1,431,518 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0012 ( 0 hom., cov: 22)

Exomes 𝑓: 0.0014 ( 3 hom. )

Consequence

C6orf132
NM_001164446.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.647

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=0.004543543).

BS2

High Homozygotes in GnomAdExome4 at 3 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.725C>T	p.Pro242Leu	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.725C>T	p.Pro242Leu	missense	Exon 4 of 5	ENSP00000341368.4	Q5T0Z8-1
C6orf132	ENST00000696229.1		n.*1337C>T		non_coding_transcript_exon	Exon 5 of 6	ENSP00000512495.1	Q5T0Z8-2
C6orf132	ENST00000696229.1		n.*1337C>T		3_prime_UTR	Exon 5 of 6	ENSP00000512495.1	Q5T0Z8-2

Frequencies

GnomAD3 genomes

AF:

0.00117

AC:

174

AN:

148874

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000998

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00127

Gnomad ASJ

AF:

0.00899

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00143

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00152

Gnomad OTH

AF:

0.00147

GnomAD2 exomes

AF:

0.00113

AC:

AN:

63104

AF XY:

0.00112

show subpopulations

Gnomad AFR exome

AF:

0.000339

Gnomad AMR exome

AF:

0.00115

Gnomad ASJ exome

AF:

0.00853

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00138

Gnomad OTH exome

AF:

0.00196

GnomAD4 exome

AF:

0.00139

AC:

1782

AN:

1282526

Hom.:

Cov.:

AF XY:

0.00138

AC XY:

858

AN XY:

621140

show subpopulations

African (AFR)

AF:

0.000142

AC:

AN:

28192

American (AMR)

AF:

0.00139

AC:

AN:

19458

Ashkenazi Jewish (ASJ)

AF:

0.00925

AC:

174

AN:

18802

East Asian (EAS)

AF:

0.00

AC:

AN:

34556

South Asian (SAS)

AF:

0.0000482

AC:

AN:

62256

European-Finnish (FIN)

AF:

0.00110

AC:

AN:

30858

Middle Eastern (MID)

AF:

0.00135

AC:

AN:

5204

European-Non Finnish (NFE)

AF:

0.00141

AC:

1456

AN:

1029796

Other (OTH)

AF:

0.00144

AC:

AN:

53404

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

195

292

390

487

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

132

198

264

330

<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:

0.00117

AC:

174

AN:

148992

Hom.:

Cov.:

AF XY:

0.00112

AC XY:

AN XY:

72622

show subpopulations

African (AFR)

AF:

0.0000995

AC:

AN:

40196

American (AMR)

AF:

0.00127

AC:

AN:

14936

Ashkenazi Jewish (ASJ)

AF:

0.00899

AC:

AN:

3450

East Asian (EAS)

AF:

0.00

AC:

AN:

4954

South Asian (SAS)

AF:

0.00

AC:

AN:

4510

European-Finnish (FIN)

AF:

0.00143

AC:

AN:

10478

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00152

AC:

102

AN:

67212

Other (OTH)

AF:

0.00145

AC:

AN:

2062

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.530

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:

0.00127

Hom.:

Bravo

AF:

0.00111

ExAC

AF:

0.000783

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

0.079

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.50

CADD

Benign

(source)

DANN

Benign

0.16

DEOGEN2

Benign

0.049

Eigen

Benign

-0.83

Eigen_PC

Benign

-0.88

FATHMM_MKL

Benign

0.48

LIST_S2

Benign

0.54

MetaRNN

Benign

0.0045

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.83

PhyloP100

0.65

PROVEAN

Pathogenic

-5.0

REVEL

Benign

0.047

Sift

Pathogenic

0.0

Sift4G

Benign

0.14

Vest4

0.16

MVP

0.14

ClinPred

0.056

GERP RS

0.70

Varity_R

0.17

gMVP

0.088

Mutation Taster

=90/10

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

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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