Variant 11-85648028-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_032273.4(TMEM126A):c.-69T>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0589 in 150,166 control chromosomes in the GnomAD database, including 838 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.059 ( 838 hom., cov: 32)

Exomes 𝑓: 0.0052 ( 0 hom. )

Consequence

TMEM126A
NM_032273.4 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.01

Variant links:

Genes affected

TMEM126A (HGNC:25382): (transmembrane protein 126A) The protein encoded by this gene is a mitochondrial membrane protein of unknown function. Defects in this gene are a cause of optic atrophy type 7 (OPA7). Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2011]

TMEM126A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.67).

BP6

Variant 11-85648028-T-A is Benign according to our data. Variant chr11-85648028-T-A is described in ClinVar as [Benign]. Clinvar id is 306320.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.202 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM126A	NM_032273.4 link	c.-69T>A		5_prime_UTR_variant	1/5	ENST00000304511.7	NP_115649.1	Q9H061-1
TMEM126A	NM_001244735.2 link	c.-186T>A		5_prime_UTR_variant	1/4		NP_001231664.1	Q9H061-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM126A	ENST00000304511 link	c.-69T>A		5_prime_UTR_variant	1/5	1	NM_032273.4	ENSP00000306887.2		Q9H061-1

Frequencies

GnomAD3 genomes

AF:

0.0588

AC:

8817

AN:

149860

Hom.:

833

Cov.:

show subpopulations

Gnomad AFR

AF:

0.205

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0213

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000656

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.000325

Gnomad OTH

AF:

0.0385

GnomAD4 exome

AF:

0.00521

AC:

AN:

192

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

136

show subpopulations

Gnomad4 AFR exome

AF:

0.250

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:

0.00

GnomAD4 genome

AF:

0.0590

AC:

8850

AN:

149974

Hom.:

838

Cov.:

AF XY:

0.0576

AC XY:

4210

AN XY:

73096

show subpopulations

Gnomad4 AFR

AF:

0.206

Gnomad4 AMR

AF:

0.0213

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000438

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000325

Gnomad4 OTH

AF:

0.0381

Alfa

AF:

0.0458

Hom.:

Bravo

AF:

0.0656

Asia WGS

AF:

0.0130

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Autosomal recessive optic atrophy, OPA7 type

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 27, 2017

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 02, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

8.3

DANN

Benign

0.78

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over