NM_001329752.2:c.161C>T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_StrongBP6

The NM_001329752.2(FAM136A):​c.161C>T​(p.Ala54Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000409 in 1,552,748 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 10/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0024 ( 1 hom., cov: 34)
Exomes 𝑓: 0.00020 ( 1 hom. )

Consequence

FAM136A
NM_001329752.2 missense

Scores

1
2
11

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.640
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.0041364133).
BP6
Variant 2-70301851-G-A is Benign according to our data. Variant chr2-70301851-G-A is described in ClinVar as [Benign]. Clinvar id is 3049056.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FAM136ANM_001329752.2 linkc.161C>T p.Ala54Val 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
FAM136AENST00000430566.6 linkc.161C>T p.Ala54Val missense_variant Exon 1 of 3 3 NM_001329752.2 ENSP00000397269.1 E7EQY1

Frequencies

GnomAD3 genomes
AF:
0.00234
AC:
356
AN:
152266
Hom.:
1
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.00825
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000588
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00191
GnomAD3 exomes
AF:
0.000487
AC:
74
AN:
151876
Hom.:
0
AF XY:
0.000323
AC XY:
26
AN XY:
80528
show subpopulations
Gnomad AFR exome
AF:
0.00788
Gnomad AMR exome
AF:
0.000202
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000230
GnomAD4 exome
AF:
0.000196
AC:
275
AN:
1400364
Hom.:
1
Cov.:
66
AF XY:
0.000140
AC XY:
97
AN XY:
690964
show subpopulations
Gnomad4 AFR exome
AF:
0.00751
Gnomad4 AMR exome
AF:
0.000196
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000278
Gnomad4 OTH exome
AF:
0.000413
GnomAD4 genome
AF:
0.00236
AC:
360
AN:
152384
Hom.:
1
Cov.:
34
AF XY:
0.00211
AC XY:
157
AN XY:
74524
show subpopulations
Gnomad4 AFR
AF:
0.00832
Gnomad4 AMR
AF:
0.000588
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:
0.00189
Alfa
AF:
0.00171
Hom.:
1
Bravo
AF:
0.00246
ExAC
AF:
0.000559
AC:
63
Asia WGS
AF:
0.00202
AC:
7
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

FAM136A-related disorder Benign:1
May 15, 2020
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
-0.33
T
BayesDel_noAF
Benign
-0.24
CADD
Benign
15
DANN
Uncertain
0.99
Eigen
Benign
-0.60
Eigen_PC
Benign
-0.81
FATHMM_MKL
Benign
0.056
N
LIST_S2
Benign
0.49
T;T
MetaRNN
Benign
0.0041
T;T
MetaSVM
Benign
-0.97
T
PROVEAN
Benign
-0.33
N;N
REVEL
Benign
0.016
Sift
Pathogenic
0.0
D;D
Sift4G
Uncertain
0.023
D;.
Vest4
0.23
MVP
0.014
ClinPred
0.081
T
GERP RS
0.66
gMVP
0.046

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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.

Other links and lift over

dbSNP: rs111492861; hg19: chr2-70528983; API