11-85648210-A-G

Position:

• chr11-85648210-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_032273.4(TMEM126A):​c.-8+121A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.203 in 152,188 control chromosomes in the GnomAD database, including 3,986 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.20 (3986 hom., cov: 32)
  • Exomes 𝑓: 0.17 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TMEM126A NM_032273.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.695

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 11-85648210-A-G is Benign according to our data. Variant chr11-85648210-A-G is described in ClinVar as [Benign]. Clinvar id is 1292287.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.347 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM126A	NM_032273.4	c.-8+121A>G		intron_variant	Intron 1 of 4	ENST00000304511.7	NP_115649.1
TMEM126A	NM_001244735.2	c.-125+121A>G		intron_variant	Intron 1 of 3		NP_001231664.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM126A	ENST00000304511.7	c.-8+121A>G		intron_variant	Intron 1 of 4	1	NM_032273.4	ENSP00000306887.2

Frequencies

GnomAD3 genomes AF: 0.202 AC: 30788 AN: 152070 Hom.: 3956 Cov.: 32

Gnomad AFR AF: 0.351

Gnomad AMI AF: 0.133

Gnomad AMR AF: 0.232

Gnomad ASJ AF: 0.112

Gnomad EAS AF: 0.286

Gnomad SAS AF: 0.284

Gnomad FIN AF: 0.148

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.108

Gnomad OTH AF: 0.186

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.167 AC: 2 AN: 12 Hom.: 0 AF XY: 0.167 AC XY: 2 AN XY: 12

Gnomad4 NFE exome AF: 0.167

GnomAD4 genome AF: 0.203 AC: 30876 AN: 152188 Hom.: 3986 Cov.: 32 AF XY: 0.208 AC XY: 15451 AN XY: 74428

Gnomad4 AFR AF: 0.352

Gnomad4 AMR AF: 0.233

Gnomad4 ASJ AF: 0.112

Gnomad4 EAS AF: 0.286

Gnomad4 SAS AF: 0.284

Gnomad4 FIN AF: 0.148

Gnomad4 NFE AF: 0.108

Gnomad4 OTH AF: 0.188

Alfa AF: 0.139 Hom.: 933

Bravo AF: 0.218

Asia WGS AF: 0.319 AC: 1108 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 23, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.8
DANN	Benign	0.61

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: rs2290823; hg19: chr11-85359254;