chr9-35045465-G-C

Variant summary

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

The ENST00000312292.6(C9orf131):ā€‹c.2836G>Cā€‹(p.Glu946Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,718 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0000048 ( 0 hom. )

Consequence

C9orf131
ENST00000312292.6 missense

Scores

2
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.25
Variant links:
Genes affected
C9orf131 (HGNC:31418): (SPATA31 subfamily G member 1)

Genome browser will be placed here

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=0.09470606).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
C9orf131NM_203299.4 linkuse as main transcriptc.2836G>C p.Glu946Gln missense_variant 2/2 ENST00000312292.6 NP_976044.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
C9orf131ENST00000312292.6 linkuse as main transcriptc.2836G>C p.Glu946Gln missense_variant 2/21 NM_203299.4 ENSP00000308279 P2Q5VYM1-1
C9orf131ENST00000421362.6 linkuse as main transcriptc.2692G>C p.Glu898Gln missense_variant 3/34 ENSP00000393683 A2Q5VYM1-2
C9orf131ENST00000354479.5 linkuse as main transcriptc.2617G>C p.Glu873Gln missense_variant 2/22 ENSP00000346472 A2Q5VYM1-3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000479
AC:
7
AN:
1461718
Hom.:
0
Cov.:
34
AF XY:
0.00000825
AC XY:
6
AN XY:
727168
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000540
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378
ExAC
AF:
0.00000824
AC:
1

ClinVar

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

Submissions by phenotype

not provided Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingARUP Laboratories, Molecular Genetics and Genomics, ARUP LaboratoriesOct 16, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.14
BayesDel_addAF
Benign
-0.26
T
BayesDel_noAF
Benign
-0.62
CADD
Benign
6.6
DANN
Uncertain
0.99
DEOGEN2
Benign
0.0096
.;.;T
Eigen
Benign
-0.33
Eigen_PC
Benign
-0.52
FATHMM_MKL
Benign
0.11
N
LIST_S2
Benign
0.57
T;T;T
M_CAP
Benign
0.0048
T
MetaRNN
Benign
0.095
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.4
.;.;M
MutationTaster
Benign
1.0
N;N;N
PROVEAN
Benign
-1.8
N;N;N
REVEL
Benign
0.046
Sift
Benign
0.12
T;T;T
Sift4G
Benign
0.35
T;T;T
Polyphen
0.96
.;.;D
Vest4
0.10
MutPred
0.14
.;.;Gain of methylation at K944 (P = 0.0963);
MVP
0.030
MPC
0.047
ClinPred
0.63
D
GERP RS
2.5
Varity_R
0.068
gMVP
0.21

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: rs780819630; hg19: chr9-35045462; API