Genetic Variant C6orf132:p.Pro242Leu (chr6-42107187-G-A) – 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.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. 12/18 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

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=0.004543543).

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C6orf132	NM_001164446.3 link	c.725C>T	p.Pro242Leu	missense_variant	Exon 4 of 5	ENST00000341865.9	NP_001157918.1	Q5T0Z8-1
C6orf132	XM_047419258.1 link	c.170C>T	p.Pro57Leu	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.725C>T	p.Pro242Leu	missense_variant	Exon 4 of 5	5	NM_001164446.3	ENSP00000341368.4	Q5T0Z8-1
C6orf132	ENST00000696229.1 link	n.*1337C>T		non_coding_transcript_exon_variant	Exon 5 of 6			ENSP00000512495.1	Q5T0Z8-2
C6orf132	ENST00000696229.1 link	n.*1337C>T		3_prime_UTR_variant	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

GnomAD3 exomes

AF:

0.00113

AC:

AN:

63104

Hom.:

AF XY:

0.00112

AC XY:

AN XY:

31342

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 SAS 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

Gnomad4 AFR exome

AF:

0.000142

Gnomad4 AMR exome

AF:

0.00139

Gnomad4 ASJ exome

AF:

0.00925

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000482

Gnomad4 FIN exome

AF:

0.00110

Gnomad4 NFE exome

AF:

0.00141

Gnomad4 OTH exome

AF:

0.00144

GnomAD4 genome

AF:

0.00117

AC:

174

AN:

148992

Hom.:

Cov.:

AF XY:

0.00112

AC XY:

AN XY:

72622

show subpopulations

Gnomad4 AFR

AF:

0.0000995

Gnomad4 AMR

AF:

0.00127

Gnomad4 ASJ

AF:

0.00899

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00143

Gnomad4 NFE

AF:

0.00152

Gnomad4 OTH

AF:

0.00145

Alfa

AF:

0.00127

Hom.:

Bravo

AF:

0.00111

ExAC

AF:

0.000783

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jun 11, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.725C>T (p.P242L) alteration is located in exon 4 (coding exon 4) of the C6orf132 gene. This alteration results from a C to T substitution at nucleotide position 725, causing the proline (P) at amino acid position 242 to be replaced by a leucine (L). 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

0.079

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.50

CADD

Benign

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

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

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