Variant 9-35045566-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The ENST00000312292.6(C9orf131):c.2937C>A(p.Ser979Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000752 in 1,461,878 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

C9orf131
ENST00000312292.6 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.309

Variant links:

Genes affected

C9orf131 (HGNC:31418): (SPATA31 subfamily G member 1)

C9orf131 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.019129425).

BP6

Variant 9-35045566-C-A is Benign according to our data. Variant chr9-35045566-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 2237994.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C9orf131	NM_203299.4 linkuse as main transcript	c.2937C>A	p.Ser979Arg	missense_variant	2/2	ENST00000312292.6	NP_976044.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C9orf131	ENST00000312292.6 linkuse as main transcript	c.2937C>A	p.Ser979Arg	missense_variant	2/2	1	NM_203299.4	ENSP00000308279	P2	Q5VYM1-1
C9orf131	ENST00000421362.6 linkuse as main transcript	c.2793C>A	p.Ser931Arg	missense_variant	3/3	4		ENSP00000393683	A2	Q5VYM1-2
C9orf131	ENST00000354479.5 linkuse as main transcript	c.2718C>A	p.Ser906Arg	missense_variant	2/2	2		ENSP00000346472	A2	Q5VYM1-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000752

AC:

AN:

1461878

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

727242

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000989

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 15, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.18

DANN

Benign

0.59

DEOGEN2

Benign

0.0014

.;.;T

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.0025

LIST_S2

Benign

0.60

T;T;T

M_CAP

Benign

0.0017

MetaRNN

Benign

0.019

T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-2.1

.;.;N

MutationTaster

Benign

1.0

N;N;N

PROVEAN

Benign

2.8

N;N;N

REVEL

Benign

0.023

Sift

Benign

1.0

T;T;T

Sift4G

Benign

1.0

T;T;T

Polyphen

0.0

.;.;B

Vest4

0.085

MutPred

0.20

.;.;Gain of MoRF binding (P = 0.0172);

MVP

0.014

MPC

0.012

ClinPred

0.094

GERP RS

-1.7

Varity_R

0.045

gMVP

0.070

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