rs2196168

Variant summary

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

The NM_032273.4(TMEM126A):c.395+10A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.238 in 1,593,950 control chromosomes in the GnomAD database, including 50,401 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.29 ( 6837 hom., cov: 33)

Exomes 𝑓: 0.23 ( 43564 hom. )

Consequence

TMEM126A
NM_032273.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.0600

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=-0.79).

BP6

Variant 11-85655718-A-G is Benign according to our data. Variant chr11-85655718-A-G is described in ClinVar as [Benign]. Clinvar id is 262022.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-85655718-A-G is described in Lovd as [Likely_benign]. Variant chr11-85655718-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.393 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM126A	NM_032273.4 linkuse as main transcript	c.395+10A>G		intron_variant		ENST00000304511.7
TMEM126A	NM_001244735.2 linkuse as main transcript	c.185+10A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM126A	ENST00000304511.7 linkuse as main transcript	c.395+10A>G		intron_variant		1	NM_032273.4	P1	Q9H061-1

Frequencies

GnomAD3 genomes

AF:

0.286

AC:

43388

AN:

151912

Hom.:

6796

Cov.:

show subpopulations

Gnomad AFR

AF:

0.398

Gnomad AMI

AF:

0.173

Gnomad AMR

AF:

0.327

Gnomad ASJ

AF:

0.234

Gnomad EAS

AF:

0.390

Gnomad SAS

AF:

0.398

Gnomad FIN

AF:

0.268

Gnomad MID

AF:

0.218

Gnomad NFE

AF:

0.200

Gnomad OTH

AF:

0.272

GnomAD3 exomes

AF:

0.290

AC:

72759

AN:

251040

Hom.:

11956

AF XY:

0.284

AC XY:

38483

AN XY:

135690

show subpopulations

Gnomad AFR exome

AF:

0.398

Gnomad AMR exome

AF:

0.428

Gnomad ASJ exome

AF:

0.244

Gnomad EAS exome

AF:

0.374

Gnomad SAS exome

AF:

0.390

Gnomad FIN exome

AF:

0.274

Gnomad NFE exome

AF:

0.200

Gnomad OTH exome

AF:

0.261

GnomAD4 exome

AF:

0.233

AC:

336366

AN:

1441918

Hom.:

43564

Cov.:

AF XY:

0.237

AC XY:

170121

AN XY:

718714

show subpopulations

Gnomad4 AFR exome

AF:

0.398

Gnomad4 AMR exome

AF:

0.418

Gnomad4 ASJ exome

AF:

0.244

Gnomad4 EAS exome

AF:

0.395

Gnomad4 SAS exome

AF:

0.384

Gnomad4 FIN exome

AF:

0.269

Gnomad4 NFE exome

AF:

0.200

Gnomad4 OTH exome

AF:

0.252

GnomAD4 genome

AF:

0.286

AC:

43487

AN:

152032

Hom.:

6837

Cov.:

AF XY:

0.294

AC XY:

21863

AN XY:

74318

show subpopulations

Gnomad4 AFR

AF:

0.398

Gnomad4 AMR

AF:

0.328

Gnomad4 ASJ

AF:

0.234

Gnomad4 EAS

AF:

0.389

Gnomad4 SAS

AF:

0.397

Gnomad4 FIN

AF:

0.268

Gnomad4 NFE

AF:

0.200

Gnomad4 OTH

AF:

0.273

Alfa

AF:

0.251

Hom.:

1770

Bravo

AF:

0.296

Asia WGS

AF:

0.419

AC:

1457

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Feb 19, 2016	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Autosomal recessive optic atrophy, OPA7 type

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

Cadd

Benign

6.6

Dann

Benign

0.74

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