chr2-70297379-ACTGT-A

Position:

• chr2-70297379-ACTGT-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_001329752.2(FAM136A):​c.644_647del​(p.Asp215ValfsTer3) variant causes a frameshift change. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.040 (0 hom., cov: 28)
  • Exomes 𝑓: 0.019 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FAM136A NM_001329752.2 frameshift
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 5.50

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• BP6: Variant 2-70297379-ACTGT-A is Benign according to our data. Variant chr2-70297379-ACTGT-A is described in ClinVar as [Likely_benign]. Clinvar id is 2651013.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAM136A	NM_001329752.2	c.644_647del	p.Asp215ValfsTer3	frameshift_variant	3/3	ENST00000430566.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM136A	ENST00000430566.6	c.644_647del	p.Asp215ValfsTer3	frameshift_variant	3/3	3	NM_001329752.2

Frequencies

GnomAD3 genomes AF: 0.00 AC: 4431 AN: 109476 Hom.: 0 Cov.: 28 FAILED QC

Gnomad AFR AF: 0.0220

Gnomad AMI AF: 0.107

Gnomad AMR AF: 0.0552

Gnomad ASJ AF: 0.0505

Gnomad EAS AF: 0.0500

Gnomad SAS AF: 0.0355

Gnomad FIN AF: 0.0388

Gnomad MID AF: 0.0126

Gnomad NFE AF: 0.0492

Gnomad OTH AF: 0.0426

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0190 AC: 19218 AN: 1012300 Hom.: 0 AF XY: 0.0185 AC XY: 9398 AN XY: 507350

Gnomad4 AFR exome AF: 0.00462

Gnomad4 AMR exome AF: 0.0222

Gnomad4 ASJ exome AF: 0.0103

Gnomad4 EAS exome AF: 0.0182

Gnomad4 SAS exome AF: 0.0110

Gnomad4 FIN exome AF: 0.00506

Gnomad4 NFE exome AF: 0.0214

Gnomad4 OTH exome AF: 0.0166

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0405 AC: 4433 AN: 109560 Hom.: 0 Cov.: 28 AF XY: 0.0417 AC XY: 2256 AN XY: 54050

Gnomad4 AFR AF: 0.0220

Gnomad4 AMR AF: 0.0552

Gnomad4 ASJ AF: 0.0505

Gnomad4 EAS AF: 0.0505

Gnomad4 SAS AF: 0.0355

Gnomad4 FIN AF: 0.0388

Gnomad4 NFE AF: 0.0492

Gnomad4 OTH AF: 0.0419

Alfa AF: 0.0471 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Aug 01, 2023

FAM136A: BS1 -

Computational scores

Source: dbNSFP v4.3

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

LitVar

Other links and lift over

dbSNP: rs761817680; hg19: chr2-70524511;