chr11-85629419-G-A

Position:

• chr11-85629419-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_018480.7(TMEM126B):​c.81+731G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0157 in 152,310 control chromosomes in the GnomAD database, including 28 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.016 (28 hom., cov: 32)
• Consequence: TMEM126B NM_018480.7 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.56

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=-0.87).
• BP6: Variant 11-85629419-G-A is Benign according to our data. Variant chr11-85629419-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1218019.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0157 (2385/152310) while in subpopulation NFE AF= 0.0231 (1573/68022). AF 95% confidence interval is 0.0222. There are 28 homozygotes in gnomad4. There are 1184 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 28 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM126B	NM_018480.7	c.81+731G>A		intron_variant		ENST00000358867.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM126B	ENST00000358867.11	c.81+731G>A		intron_variant		2	NM_018480.7	P1

Frequencies

GnomAD3 genomes AF: 0.0157 AC: 2387 AN: 152192 Hom.: 28 Cov.: 32

Gnomad AFR AF: 0.00405

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.0160

Gnomad ASJ AF: 0.0112

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00952

Gnomad FIN AF: 0.0247

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0231

Gnomad OTH AF: 0.0211

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

GnomAD4 genome AF: 0.0157 AC: 2385 AN: 152310 Hom.: 28 Cov.: 32 AF XY: 0.0159 AC XY: 1184 AN XY: 74482

Gnomad4 AFR AF: 0.00404

Gnomad4 AMR AF: 0.0159

Gnomad4 ASJ AF: 0.0112

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00911

Gnomad4 FIN AF: 0.0247

Gnomad4 NFE AF: 0.0231

Gnomad4 OTH AF: 0.0213

Alfa AF: 0.0200 Hom.: 6

Bravo AF: 0.0139

Asia WGS AF: 0.00346 AC: 13 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 07, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.8
DANN	Benign	0.51

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: rs7947489; hg19: chr11-85340463;