rs566955361

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001329752.2(FAM136A):​c.385C>T​(p.Pro129Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000013 in 1,535,794 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/14 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

FAM136A
NM_001329752.2 missense

Scores

1
14

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.468
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 -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.051442444).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FAM136ANM_001329752.2 linkc.385C>T p.Pro129Ser 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.385C>T p.Pro129Ser missense_variant Exon 1 of 3 3 NM_001329752.2 ENSP00000397269.1 E7EQY1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152234
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
7.23e-7
AC:
1
AN:
1383560
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
682740
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000173
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152234
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
74370
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.20
T
BayesDel_noAF
Benign
-0.53
CADD
Benign
6.0
DANN
Uncertain
0.99
Eigen
Benign
-0.84
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.021
N
LIST_S2
Benign
0.40
T
M_CAP
Benign
0.00053
T
MetaRNN
Benign
0.051
T
MetaSVM
Benign
-1.0
T
PROVEAN
Benign
1.3
N
REVEL
Benign
0.0090
Sift
Benign
0.98
T
Sift4G
Benign
0.51
T
Vest4
0.20
MutPred
0.29
Gain of phosphorylation at P129 (P = 0.0304);
MVP
0.014
ClinPred
0.082
T
GERP RS
-1.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
2.2
gMVP
0.072

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.11
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: rs566955361; hg19: chr2-70528759; API