dbSNP rs10501595: TMEM126B:c.203+107T>C (chr11-85631915-T-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_018480.7(TMEM126B):c.203+107T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 1,207,450 control chromosomes in the GnomAD database, including 9,997 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 1481 hom., cov: 32)

Exomes 𝑓: 0.11 ( 8516 hom. )

Consequence

TMEM126B
NM_018480.7 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0200

Variant links:

Genes affected

TMEM126B (HGNC:30883): (transmembrane protein 126B) This gene encodes a mitochondrial transmembrane protein which is a component of the mitochondrial complex I assembly complex. The encoded protein serves as an assembly factor that is required for formation of the membrane arm of the complex. It interacts with NADH dehydrogenase [ubiquinone] 1 alpha subcomplex assembly factor 13. Naturally occurring mutations in this gene are associated with isolated complex I deficiency. A pseudogene of this gene has been defined on chromosome 9. [provided by RefSeq, Apr 2017]

TMEM126B 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=-0.86).

BP6

Variant 11-85631915-T-C is Benign according to our data. Variant chr11-85631915-T-C is described in ClinVar as [Benign]. Clinvar id is 671604.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.273 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM126B	NM_018480.7 link	c.203+107T>C		intron_variant	Intron 2 of 4	ENST00000358867.11	NP_060950.3	Q8IUX1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM126B	ENST00000358867.11 link	c.203+107T>C		intron_variant	Intron 2 of 4	2	NM_018480.7	ENSP00000351737.7		Q8IUX1-1

Frequencies

GnomAD3 genomes

AF:

0.127

AC:

19305

AN:

152058

Hom.:

1468

Cov.:

show subpopulations

Gnomad AFR

AF:

0.126

Gnomad AMI

AF:

0.0844

Gnomad AMR

AF:

0.198

Gnomad ASJ

AF:

0.0958

Gnomad EAS

AF:

0.285

Gnomad SAS

AF:

0.259

Gnomad FIN

AF:

0.136

Gnomad MID

AF:

0.111

Gnomad NFE

AF:

0.0909

Gnomad OTH

AF:

0.129

GnomAD4 exome

AF:

0.113

AC:

119182

AN:

1055272

Hom.:

8516

AF XY:

0.116

AC XY:

60615

AN XY:

521358

show subpopulations

African (AFR)

AF:

0.121

AC:

2769

AN:

22866

American (AMR)

AF:

0.264

AC:

4501

AN:

17018

Ashkenazi Jewish (ASJ)

AF:

0.0997

AC:

1685

AN:

16904

East Asian (EAS)

AF:

0.280

AC:

8757

AN:

31234

South Asian (SAS)

AF:

0.247

AC:

13124

AN:

53208

European-Finnish (FIN)

AF:

0.138

AC:

4725

AN:

34244

Middle Eastern (MID)

AF:

0.0909

AC:

288

AN:

3170

European-Non Finnish (NFE)

AF:

0.0935

AC:

77742

AN:

831906

Other (OTH)

AF:

0.125

AC:

5591

AN:

44722

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

4777

9554

14331

19108

23885

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.127

AC:

19352

AN:

152178

Hom.:

1481

Cov.:

AF XY:

0.134

AC XY:

9942

AN XY:

74402

show subpopulations

African (AFR)

AF:

0.126

AC:

5251

AN:

41530

American (AMR)

AF:

0.198

AC:

3034

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.0958

AC:

332

AN:

3466

East Asian (EAS)

AF:

0.285

AC:

1478

AN:

5178

South Asian (SAS)

AF:

0.259

AC:

1248

AN:

4824

European-Finnish (FIN)

AF:

0.136

AC:

1438

AN:

10584

Middle Eastern (MID)

AF:

0.102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0910

AC:

6186

AN:

67998

Other (OTH)

AF:

0.132

AC:

278

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

812

1624

2437

3249

4061

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.106

Hom.:

133

Bravo

AF:

0.135

Asia WGS

AF:

0.292

AC:

1013

AN:

3470

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jun 16, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

2.9

(source)

DANN

Benign

0.62

PhyloP100

0.020

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

LitVar

Below is the list of publications found by LitVar for variant 11:85631915 T>C . It may be empty.

rs10501595

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over