Variant 2-70301905-T-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.107A>C(p.Asn36Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00133 in 1,599,178 control chromosomes in the GnomAD database, including 10 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 0.0044 ( 5 hom., cov: 34)

Exomes 𝑓: 0.0010 ( 5 hom. )

Consequence

FAM136A
NM_001329752.2 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -3.50

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:

ENSG00000233849 (HGNC:):

ENSG00000233849 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=0.004153043).

BP6

Variant 2-70301905-T-G is Benign according to our data. Variant chr2-70301905-T-G is described in ClinVar as [Benign]. Clinvar id is 3042819.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM136A	NM_001329752.2 link	c.107A>C	p.Asn36Thr	missense_variant	Exon 1 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.107A>C	p.Asn36Thr	missense_variant	Exon 1 of 3	3	NM_001329752.2	ENSP00000397269.1		E7EQY1

Frequencies

GnomAD3 genomes

AF:

0.00438

AC:

667

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0112

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00798

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000838

Gnomad OTH

AF:

0.00813

GnomAD3 exomes

AF:

0.00149

AC:

330

AN:

220852

Hom.:

AF XY:

0.00113

AC XY:

136

AN XY:

119824

show subpopulations

Gnomad AFR exome

AF:

0.00893

Gnomad AMR exome

AF:

0.00304

Gnomad ASJ exome

AF:

0.000107

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000108

Gnomad FIN exome

AF:

0.0000513

Gnomad NFE exome

AF:

0.000938

Gnomad OTH exome

AF:

0.00309

GnomAD4 exome

AF:

0.00101

AC:

1467

AN:

1446824

Hom.:

Cov.:

AF XY:

0.000926

AC XY:

665

AN XY:

718296

show subpopulations

Gnomad4 AFR exome

AF:

0.0110

Gnomad4 AMR exome

AF:

0.00317

Gnomad4 ASJ exome

AF:

0.0000776

Gnomad4 EAS exome

AF:

0.0000256

Gnomad4 SAS exome

AF:

0.0000954

Gnomad4 FIN exome

AF:

0.0000771

Gnomad4 NFE exome

AF:

0.000694

Gnomad4 OTH exome

AF:

0.00248

GnomAD4 genome

AF:

0.00438

AC:

667

AN:

152354

Hom.:

Cov.:

AF XY:

0.00442

AC XY:

329

AN XY:

74514

show subpopulations

Gnomad4 AFR

AF:

0.0112

Gnomad4 AMR

AF:

0.00797

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.000838

Gnomad4 OTH

AF:

0.00804

Alfa

AF:

0.00220

Hom.:

Bravo

AF:

0.00520

ESP6500AA

AF:

0.00841

AC:

ESP6500EA

AF:

0.000698

AC:

ExAC

AF:

0.00150

AC:

182

Asia WGS

AF:

0.000866

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

Jan 13, 2021

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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

-0.51

BayesDel_noAF

Benign

-0.50

CADD

Benign

0.0090

DANN

Benign

0.81

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0046

LIST_S2

Benign

0.39

T;T

MetaRNN

Benign

0.0042

T;T

MetaSVM

Benign

-0.98

PROVEAN

Benign

-0.30

N;N

REVEL

Benign

0.033

Sift

Pathogenic

0.0

D;D

Sift4G

Uncertain

0.037

D;.

Vest4

0.28

MVP

0.014

ClinPred

0.030

GERP RS

-7.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

gMVP

0.029

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