rs80356558

Positions:

• chrX-101345993-G-GATC

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6 BA1

The NM_004085.4(TIMM8A):​c.*505_*506insGAT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.37 (8763 hom., 11391 hem., cov: 11)
  • Exomes 𝑓: 0.18 (10090 hom. 33384 hem.)
  • Failed GnomAD Quality Control
• Consequence: TIMM8A NM_004085.4 3_prime_UTR
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 1.37

Genes affected

TIMM8A (HGNC:11817): (translocase of inner mitochondrial membrane 8A) This translocase is involved in the import and insertion of hydrophobic membrane proteins from the cytoplasm into the mitochondrial inner membrane. The gene is mutated in Mohr-Tranebjaerg syndrome/Deafness Dystonia Syndrome (MTS/DDS) and it is postulated that MTS/DDS is a mitochondrial disease caused by a defective mitochondrial protein import system. Defects in this gene also cause Jensen syndrome; an X-linked disease with opticoacoustic nerve atrophy and muscle weakness. This protein, along with TIMM13, forms a 70 kDa heterohexamer. Alternative splicing results in multiple transcript variants encoding distinct isoforms.[provided by RefSeq, Mar 2009]

ACMG classification

Verdict is Benign. Variant got -9 ACMG points.

• BP6: Variant X-101345993-G-GATC is Benign according to our data. Variant chrX-101345993-G-GATC is described in ClinVar as [Benign]. Clinvar id is 21394.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.795 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TIMM8A	NM_004085.4	c.*505_*506insGAT		3_prime_UTR_variant	2/2	ENST00000372902.4	NP_004076.1
TIMM8A	NM_001145951.2	c.*2393_*2394insGAT		3_prime_UTR_variant	2/2		NP_001139423.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TIMM8A	ENST00000372902.4	c.*505_*506insGAT		3_prime_UTR_variant	2/2	1	NM_004085.4	ENSP00000361993	P1
TIMM8A	ENST00000644112.2	c.*2393_*2394insGAT		3_prime_UTR_variant	2/2			ENSP00000494385
TIMM8A	ENST00000647480.1	n.1316_1317insGAT		non_coding_transcript_exon_variant	2/2
TIMM8A	ENST00000645279.1	c.*993_*994insGAT		3_prime_UTR_variant, NMD_transcript_variant	3/3			ENSP00000494239

Frequencies

GnomAD3 genomes AF: 0.369 AC: 40476 AN: 109769 Hom.: 8757 Cov.: 11 AF XY: 0.353 AC XY: 11339 AN XY: 32127

Gnomad AFR AF: 0.804

Gnomad AMI AF: 0.0948

Gnomad AMR AF: 0.366

Gnomad ASJ AF: 0.155

Gnomad EAS AF: 0.437

Gnomad SAS AF: 0.441

Gnomad FIN AF: 0.152

Gnomad MID AF: 0.186

Gnomad NFE AF: 0.156

Gnomad OTH AF: 0.315

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.177 AC: 113854 AN: 642029 Hom.: 10090 Cov.: 19 AF XY: 0.174 AC XY: 33384 AN XY: 191905

Gnomad4 AFR exome AF: 0.844

Gnomad4 AMR exome AF: 0.422

Gnomad4 ASJ exome AF: 0.160

Gnomad4 EAS exome AF: 0.442

Gnomad4 SAS exome AF: 0.447

Gnomad4 FIN exome AF: 0.159

Gnomad4 NFE exome AF: 0.154

Gnomad4 OTH exome AF: 0.233

GnomAD4 genome AF: 0.369 AC: 40540 AN: 109823 Hom.: 8763 Cov.: 11 AF XY: 0.354 AC XY: 11391 AN XY: 32193

Gnomad4 AFR AF: 0.804

Gnomad4 AMR AF: 0.366

Gnomad4 ASJ AF: 0.155

Gnomad4 EAS AF: 0.437

Gnomad4 SAS AF: 0.440

Gnomad4 FIN AF: 0.152

Gnomad4 NFE AF: 0.156

Gnomad4 OTH AF: 0.319

Alfa AF: 0.306 Hom.: 1886

Bravo AF: 0.414

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

Deafness dystonia syndrome Benign:1

Benign, no assertion criteria provided

curation

GeneReviews

Feb 06, 2003

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4024308; hg19: chrX-100600981;