rs569344768

Variant names:

• chr2-70301972-C-G
• NM_001329752.2:c.40G>C

Your query was ambiguous. Multiple possible variants found:

• chr2-70301972-C-G
• chr2-70301972-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001329752.2(FAM136A):​c.40G>C​(p.Glu14Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000000687 in 1,455,612 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: FAM136A NM_001329752.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.04

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]

ENSG00000233849 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19365165).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM136A	NM_001329752.2	c.40G>C	p.Glu14Gln	missense_variant	Exon 1 of 3	ENST00000430566.6	NP_001316681.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM136A	ENST00000430566.6	c.40G>C	p.Glu14Gln	missense_variant	Exon 1 of 3	3	NM_001329752.2	ENSP00000397269.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1455612 Hom.: 0 Cov.: 65 AF XY: 0.00000138 AC XY: 1 AN XY: 723826

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: 9.01e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.57
BayesDel_addAF	Benign	-0.091	T
BayesDel_noAF	Benign	-0.37
CADD	Uncertain	24
DANN	Benign	0.93
DEOGEN2	Benign	0.0083	T;.
Eigen	Uncertain	0.19
Eigen_PC	Benign	0.15
FATHMM_MKL	Benign	0.65	D
LIST_S2	Benign	0.63	T;T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.19	T;T
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	1.7	L;.
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-0.89	N;N
REVEL	Benign	0.15
Sift	Benign	0.31	T;D
Sift4G	Benign	0.30	T;D
Polyphen		0.82	P;.
Vest4		0.21
MutPred		0.45		Gain of MoRF binding (P = 0.0225);Gain of MoRF binding (P = 0.0225);
MVP		0.014
MPC		0.19
ClinPred		0.86	D
GERP RS		3.8
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		3.7
Varity_R		0.40
gMVP		0.11

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-70529104;