NM_032273.4:c.395+10A>G

Variant names:

Variant summary

Our verdict is Benign. The variant received -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:6

Conservation

PhyloP100: 0.0600

Publications

19 publications found

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 Gene-Disease associations (from GenCC):

optic atrophy
Inheritance: AR Classification: DEFINITIVE Submitted by: G2P
autosomal recessive optic atrophy, OPA7 type
Inheritance: AR Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics

TMEM126A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 262022.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM126A	NM_032273.4 link	c.395+10A>G		intron_variant	Intron 4 of 4	ENST00000304511.7	NP_115649.1	Q9H061-1
TMEM126A	NM_001244735.2 link	c.185+10A>G		intron_variant	Intron 3 of 3		NP_001231664.1	Q9H061-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM126A	ENST00000304511.7 link	c.395+10A>G		intron_variant	Intron 4 of 4	1	NM_032273.4	ENSP00000306887.2		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

GnomAD2 exomes

AF:

0.290

AC:

72759

AN:

251040

AF XY:

0.284

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 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

African (AFR)

AF:

0.398

AC:

13173

AN:

33088

American (AMR)

AF:

0.418

AC:

18684

AN:

44658

Ashkenazi Jewish (ASJ)

AF:

0.244

AC:

6339

AN:

25986

East Asian (EAS)

AF:

0.395

AC:

15625

AN:

39518

South Asian (SAS)

AF:

0.384

AC:

32937

AN:

85812

European-Finnish (FIN)

AF:

0.269

AC:

14364

AN:

53372

Middle Eastern (MID)

AF:

0.224

AC:

1282

AN:

5722

European-Non Finnish (NFE)

AF:

0.200

AC:

218947

AN:

1094066

Other (OTH)

AF:

0.252

AC:

15015

AN:

59696

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

11969

23937

35906

47874

59843

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8026

16052

24078

32104

40130

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.286

AC:

43487

AN:

152032

Hom.:

6837

Cov.:

AF XY:

0.294

AC XY:

21863

AN XY:

74318

show subpopulations

African (AFR)

AF:

0.398

AC:

16512

AN:

41442

American (AMR)

AF:

0.328

AC:

5007

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.234

AC:

812

AN:

3468

East Asian (EAS)

AF:

0.389

AC:

2016

AN:

5176

South Asian (SAS)

AF:

0.397

AC:

1919

AN:

4828

European-Finnish (FIN)

AF:

0.268

AC:

2832

AN:

10574

Middle Eastern (MID)

AF:

0.207

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.200

AC:

13593

AN:

67948

Other (OTH)

AF:

0.273

AC:

577

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1524

3048

4573

6097

7621

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

442

884

1326

1768

2210

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.253

Hom.:

1829

Bravo

AF:

0.296

Asia WGS

AF:

0.419

AC:

1457

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 19, 2016

Mayo Clinic Laboratories, Mayo Clinic

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Autosomal recessive optic atrophy, OPA7 type

Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

(source)

DANN

Benign

0.74

PhyloP100

0.060

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over