Variant chr2-70297445-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_001329752.2(FAM136A):c.582C>T(p.Asn194Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.291 in 1,607,534 control chromosomes in the GnomAD database, including 48,517 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.26 ( 4538 hom., cov: 33)

Exomes 𝑓: 0.29 ( 43979 hom. )

Consequence

FAM136A
NM_001329752.2 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.777

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BP6

Variant 2-70297445-G-A is Benign according to our data. Variant chr2-70297445-G-A is described in ClinVar as [Benign]. Clinvar id is 3059710.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-0.777 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.338 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM136A	NM_001329752.2 link	c.582C>T	p.Asn194Asn	synonymous_variant	Exon 3 of 3	ENST00000430566.6	NP_001316681.1	E7EQY1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM136A	ENST00000430566.6 link	c.582C>T	p.Asn194Asn	synonymous_variant	Exon 3 of 3	3	NM_001329752.2	ENSP00000397269.1		E7EQY1

Frequencies

GnomAD3 genomes

AF:

0.261

AC:

39427

AN:

150872

Hom.:

4546

Cov.:

show subpopulations

Gnomad AFR

AF:

0.160

Gnomad AMI

AF:

0.308

Gnomad AMR

AF:

0.214

Gnomad ASJ

AF:

0.214

Gnomad EAS

AF:

0.353

Gnomad SAS

AF:

0.302

Gnomad FIN

AF:

0.404

Gnomad MID

AF:

0.201

Gnomad NFE

AF:

0.304

Gnomad OTH

AF:

0.258

GnomAD3 exomes

AF:

0.284

AC:

71114

AN:

250460

Hom.:

8961

AF XY:

0.287

AC XY:

38879

AN XY:

135318

show subpopulations

Gnomad AFR exome

AF:

0.160

Gnomad AMR exome

AF:

0.177

Gnomad ASJ exome

AF:

0.210

Gnomad EAS exome

AF:

0.353

Gnomad SAS exome

AF:

0.292

Gnomad FIN exome

AF:

0.406

Gnomad NFE exome

AF:

0.304

Gnomad OTH exome

AF:

0.286

GnomAD4 exome

AF:

0.294

AC:

427723

AN:

1456542

Hom.:

43979

Cov.:

AF XY:

0.294

AC XY:

212976

AN XY:

724620

show subpopulations

Gnomad4 AFR exome

AF:

0.152

Gnomad4 AMR exome

AF:

0.182

Gnomad4 ASJ exome

AF:

0.210

Gnomad4 EAS exome

AF:

0.326

Gnomad4 SAS exome

AF:

0.293

Gnomad4 FIN exome

AF:

0.399

Gnomad4 NFE exome

AF:

0.299

Gnomad4 OTH exome

AF:

0.285

GnomAD4 genome

AF:

0.261

AC:

39424

AN:

150992

Hom.:

4538

Cov.:

AF XY:

0.266

AC XY:

19622

AN XY:

73770

show subpopulations

Gnomad4 AFR

AF:

0.160

Gnomad4 AMR

AF:

0.214

Gnomad4 ASJ

AF:

0.214

Gnomad4 EAS

AF:

0.352

Gnomad4 SAS

AF:

0.304

Gnomad4 FIN

AF:

0.404

Gnomad4 NFE

AF:

0.304

Gnomad4 OTH

AF:

0.256

Alfa

AF:

0.279

Hom.:

2279

Asia WGS

AF:

0.312

AC:

1085

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

Jun 22, 2020

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_noAF

Benign

-0.68

CADD

Benign

0.50

DANN

Benign

0.84

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