Variant 2-70301656-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_001329752.2(FAM136A):c.356G>C(p.Trp119Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00053 in 1,535,386 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0028 ( 3 hom., cov: 33)

Exomes 𝑓: 0.00028 ( 3 hom. )

Consequence

FAM136A
NM_001329752.2 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.936

Variant links:

Genes affected

FAM136A (HGNC:25911): (family with sequence similarity 136 member A) This gene encodes a mitochondrially localized protein that is highly conserved across species. The gene is expressed in a variety of tissues including human lymphoblast cells and rat neurosensorial epithelium of the cristaampullaris. A mutation in this gene has been associated with familial Meniere's disease, a chronic disorder of the inner ear. Several pseudogenes of this gene are found on other chromosomes. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2016]

FAM136A links:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0037873983).

BP6

Variant 2-70301656-C-G is Benign according to our data. Variant chr2-70301656-C-G is described in ClinVar as [Benign]. Clinvar id is 3035381.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAM136A	NM_001329752.2 linkuse as main transcript	c.356G>C	p.Trp119Ser	missense_variant	1/3	ENST00000430566.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM136A	ENST00000430566.6 linkuse as main transcript	c.356G>C	p.Trp119Ser	missense_variant	1/3	3	NM_001329752.2
	ENST00000445084.1 linkuse as main transcript	n.169+37C>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.00284

AC:

432

AN:

152238

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00969

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00150

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.000554

AC:

AN:

133664

Hom.:

AF XY:

0.000384

AC XY:

AN XY:

72894

show subpopulations

Gnomad AFR exome

AF:

0.00817

Gnomad AMR exome

AF:

0.000573

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000446

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000959

Gnomad OTH exome

AF:

0.000486

GnomAD4 exome

AF:

0.000275

AC:

381

AN:

1383030

Hom.:

Cov.:

AF XY:

0.000227

AC XY:

155

AN XY:

682386

show subpopulations

Gnomad4 AFR exome

AF:

0.00899

Gnomad4 AMR exome

AF:

0.000645

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:

0.0000139

Gnomad4 OTH exome

AF:

0.000743

GnomAD4 genome

AF:

0.00284

AC:

433

AN:

152356

Hom.:

Cov.:

AF XY:

0.00272

AC XY:

203

AN XY:

74514

show subpopulations

Gnomad4 AFR

AF:

0.00969

Gnomad4 AMR

AF:

0.00150

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00137

Hom.:

Bravo

AF:

0.00293

ExAC

AF:

0.000494

AC:

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

FAM136A-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 30, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.41

CADD

Benign

1.9

DANN

Benign

0.71

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.027

LIST_S2

Benign

0.36

MetaRNN

Benign

0.0038

MetaSVM

Benign

-0.99

MutationTaster

Benign

1.0

N;N;N

PROVEAN

Benign

0.020

REVEL

Benign

0.0040

Sift

Benign

0.45

Sift4G

Benign

0.17

Vest4

0.36

MutPred

0.36

Gain of phosphorylation at W119 (P = 0.0293);

MVP

0.014

ClinPred

0.0027

GERP RS

-1.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

gMVP

0.17

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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