rs749609931

Variant names:

• chr11-85650239-GTTTT-G
• rs749609931
• NM_032273.4:c.-7-7_-7-4delTTTT

Your query was ambiguous. Multiple possible variants found:

• chr11-85650239-GTTTT-G
• chr11-85650239-GTTTT-GT
• chr11-85650239-GTTTT-GTTT

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_032273.4(TMEM126A):​c.-7-7_-7-4delTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000728 in 1,373,590 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predicting alterations to normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: TMEM126A NM_032273.4 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.94
• Publications: 0 publications found

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM126A	NM_032273.4	c.-7-7_-7-4delTTTT		splice_region_variant, intron_variant	Intron 1 of 4	ENST00000304511.7	NP_115649.1
TMEM126A	NM_001244735.2	c.-125+2153_-125+2156delTTTT		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.-7-9_-7-6delTTTT		splice_region_variant, intron_variant	Intron 1 of 4	1	NM_032273.4	ENSP00000306887.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000416 AC: 1 AN: 240164 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000303

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.28e-7 AC: 1 AN: 1373590 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 687522

African (AFR) AF: 0.00 AC: 0 AN: 31366

American (AMR) AF: 0.0000232 AC: 1 AN: 43126

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25336

East Asian (EAS) AF: 0.00 AC: 0 AN: 39114

South Asian (SAS) AF: 0.00 AC: 0 AN: 81674

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53176

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4644

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1037898

Other (OTH) AF: 0.00 AC: 0 AN: 57256

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.9

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.88		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.88		Position offset: 10

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs749609931; hg19: chr11-85361283;