6-42105519-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001164446.3(C6orf132):​c.2393G>A​(p.Gly798Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

C6orf132
NM_001164446.3 missense

Scores

1
3
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.361
Variant links:
Genes affected
C6orf132 (HGNC:21288): (chromosome 6 open reading frame 132)

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.09241673).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
C6orf132NM_001164446.3 linkc.2393G>A p.Gly798Glu missense_variant Exon 4 of 5 ENST00000341865.9 NP_001157918.1 Q5T0Z8-1
C6orf132XM_047419258.1 linkc.1838G>A p.Gly613Glu 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.2393G>A p.Gly798Glu missense_variant Exon 4 of 5 5 NM_001164446.3 ENSP00000341368.4 Q5T0Z8-1
C6orf132ENST00000696229.1 linkn.*3005G>A non_coding_transcript_exon_variant Exon 5 of 6 ENSP00000512495.1 Q5T0Z8-2
C6orf132ENST00000696229.1 linkn.*3005G>A 3_prime_UTR_variant Exon 5 of 6 ENSP00000512495.1 Q5T0Z8-2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
78
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jul 14, 2021
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.2393G>A (p.G798E) 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 2393, causing the glycine (G) at amino acid position 798 to be replaced by a glutamic acid (E). 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
-0.25
T
BayesDel_noAF
Benign
-0.59
CADD
Benign
7.5
DANN
Uncertain
0.98
DEOGEN2
Benign
0.067
T
Eigen
Benign
-0.83
Eigen_PC
Benign
-0.96
FATHMM_MKL
Benign
0.021
N
LIST_S2
Benign
0.41
T
M_CAP
Benign
0.0097
T
MetaRNN
Benign
0.092
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.14
N
PROVEAN
Uncertain
-3.8
D
REVEL
Benign
0.030
Sift
Pathogenic
0.0
D
Sift4G
Uncertain
0.0040
D
Vest4
0.065
MutPred
0.16
Gain of solvent accessibility (P = 0.024);
MVP
0.15
ClinPred
0.23
T
GERP RS
0.18
Varity_R
0.20
gMVP
0.077

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-42073257; API