6-42106902-C-T

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

2
16

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)

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
C6orf132NM_001164446.3 linkc.1010G>A p.Arg337Gln missense_variant Exon 4 of 5 ENST00000341865.9 NP_001157918.1 Q5T0Z8-1
C6orf132XM_047419258.1 linkc.455G>A p.Arg152Gln missense_variant Exon 3 of 4 XP_047275214.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
C6orf132ENST00000341865.9 linkc.1010G>A p.Arg337Gln missense_variant Exon 4 of 5 5 NM_001164446.3 ENSP00000341368.4 Q5T0Z8-1
C6orf132ENST00000696229.1 linkn.*1622G>A non_coding_transcript_exon_variant Exon 5 of 6 ENSP00000512495.1 Q5T0Z8-2
C6orf132ENST00000696229.1 linkn.*1622G>A 3_prime_UTR_variant Exon 5 of 6 ENSP00000512495.1 Q5T0Z8-2

Frequencies

GnomAD3 genomes
AF:
0.0000265
AC:
4
AN:
150992
Hom.:
0
Cov.:
26
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:
3
AN:
139178
Hom.:
0
AF XY:
0.0000268
AC XY:
2
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:
28
AN:
1383824
Hom.:
0
Cov.:
36
AF XY:
0.0000234
AC XY:
16
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:
4
AN:
150992
Hom.:
0
Cov.:
26
AF XY:
0.0000136
AC XY:
1
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
T
BayesDel_noAF
Benign
-0.53
CADD
Benign
15
DANN
Uncertain
1.0
DEOGEN2
Benign
0.011
T
Eigen
Benign
-0.72
Eigen_PC
Benign
-0.76
FATHMM_MKL
Benign
0.36
N
LIST_S2
Benign
0.48
T
M_CAP
Benign
0.029
D
MetaRNN
Benign
0.061
T
MetaSVM
Benign
-0.98
T
MutationAssessor
Benign
0.69
N
PROVEAN
Benign
-1.5
N
REVEL
Benign
0.012
Sift
Uncertain
0.022
D
Sift4G
Benign
0.45
T
Vest4
0.097
MVP
0.048
ClinPred
0.21
T
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.

Other links and lift over

dbSNP: rs1213909019; hg19: chr6-42074640; API