11-85629547-C-T

Position:

• chr11-85629547-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_018480.7(TMEM126B):​c.81+859C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 152,090 control chromosomes in the GnomAD database, including 1,378 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.12 (1378 hom., cov: 32)
• Consequence: TMEM126B NM_018480.7 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.959

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 11-85629547-C-T is Benign according to our data. Variant chr11-85629547-C-T is described in ClinVar as [Benign]. Clinvar id is 671603.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.272 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM126B	NM_018480.7	c.81+859C>T		intron_variant		ENST00000358867.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM126B	ENST00000358867.11	c.81+859C>T		intron_variant		2	NM_018480.7	P1

Frequencies

GnomAD3 genomes AF: 0.122 AC: 18591 AN: 151970 Hom.: 1365 Cov.: 32

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.0848

Gnomad AMR AF: 0.189

Gnomad ASJ AF: 0.0960

Gnomad EAS AF: 0.284

Gnomad SAS AF: 0.261

Gnomad FIN AF: 0.138

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.0905

Gnomad OTH AF: 0.126

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.123 AC: 18638 AN: 152090 Hom.: 1378 Cov.: 32 AF XY: 0.129 AC XY: 9604 AN XY: 74346

Gnomad4 AFR AF: 0.113

Gnomad4 AMR AF: 0.189

Gnomad4 ASJ AF: 0.0960

Gnomad4 EAS AF: 0.285

Gnomad4 SAS AF: 0.260

Gnomad4 FIN AF: 0.138

Gnomad4 NFE AF: 0.0905

Gnomad4 OTH AF: 0.129

Alfa AF: 0.114 Hom.: 507

Bravo AF: 0.129

Asia WGS AF: 0.288 AC: 999 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 16, 2018

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	-0.76
CADD	Benign	8.0
DANN	Benign	0.72

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

Other links and lift over

dbSNP: rs17208519; hg19: chr11-85340591;