rs552744004

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -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. 13/16 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

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

Meniere disease
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

FAM136A links:

ENSG00000233849 (HGNC:):

ENSG00000233849 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 3035381.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAd4 at 3 Unknown gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001329752.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FAM136A	NM_001329752.2	MANE Select	c.356G>C	p.Trp119Ser	missense	Exon 1 of 3	NP_001316681.1	E7EQY1
FAM136A	NM_001329753.2		c.342+14G>C		intron	N/A	NP_001316682.1
FAM136A	NM_032822.3		c.87+269G>C		intron	N/A	NP_116211.2	Q96C01

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FAM136A	ENST00000430566.6	TSL:3 MANE Select	c.356G>C	p.Trp119Ser	missense	Exon 1 of 3	ENSP00000397269.1	E7EQY1
FAM136A	ENST00000037869.8	TSL:1	c.87+269G>C		intron	N/A	ENSP00000037869.3	Q96C01
FAM136A	ENST00000460307.1	TSL:1	n.133-53G>C		intron	N/A

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

GnomAD2 exomes

AF:

0.000554

AC:

AN:

133664

AF XY:

0.000384

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 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

African (AFR)

AF:

0.00899

AC:

284

AN:

31580

American (AMR)

AF:

0.000645

AC:

AN:

35666

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25142

East Asian (EAS)

AF:

0.00

AC:

AN:

35718

South Asian (SAS)

AF:

0.0000505

AC:

AN:

79174

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33796

Middle Eastern (MID)

AF:

0.00211

AC:

AN:

5682

European-Non Finnish (NFE)

AF:

0.0000139

AC:

AN:

1078402

Other (OTH)

AF:

0.000743

AC:

AN:

57870

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

107

134

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00284

AC:

433

AN:

152356

Hom.:

Cov.:

AF XY:

0.00272

AC XY:

203

AN XY:

74514

show subpopulations

African (AFR)

AF:

0.00969

AC:

403

AN:

41594

American (AMR)

AF:

0.00150

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68032

Other (OTH)

AF:

0.00237

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

104

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00137

Hom.:

Bravo

AF:

0.00293

ExAC

AF:

0.000494

AC:

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

FAM136A-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.41

CADD

Benign

1.9

(source)

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

PhyloP100

-0.94

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

PromoterAI

0.024

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

gMVP

0.17

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over