Variant 2-70301783-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_001329752.2(FAM136A):c.229C>G(p.Leu77Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000717 in 1,394,254 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

FAM136A
NM_001329752.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.327

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09256646).

BP6

Variant 2-70301783-G-C is Benign according to our data. Variant chr2-70301783-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 1701380.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM136A	NM_001329752.2 link	c.229C>G	p.Leu77Val	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.229C>G	p.Leu77Val	missense_variant	Exon 1 of 3	3	NM_001329752.2	ENSP00000397269.1		E7EQY1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000697

AC:

AN:

143488

Hom.:

AF XY:

0.0000130

AC XY:

AN XY:

76854

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000444

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.17e-7

AC:

AN:

1394254

Hom.:

Cov.:

AF XY:

0.00000145

AC XY:

AN XY:

687598

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:

0.0000126

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jul 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

FAM136A: BP4 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.26

CADD

Benign

5.9

DANN

Benign

0.96

Eigen

Benign

-0.60

Eigen_PC

Benign

-0.79

FATHMM_MKL

Benign

0.060

LIST_S2

Benign

0.42

T;T

M_CAP

Benign

0.0015

MetaRNN

Benign

0.093

T;T

MetaSVM

Benign

-0.97

PROVEAN

Benign

-0.23

N;N

REVEL

Benign

0.018

Sift

Pathogenic

0.0

D;D

Sift4G

Benign

0.20

T;.

Vest4

0.10

MutPred

0.34

Gain of MoRF binding (P = 0.0979);.;

MVP

0.014

ClinPred

0.13

GERP RS

0.39

gMVP

0.041

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