rs7085433

Positions:

• chr10-46002468-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000580018.4(TIMM23):​c.515-735C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 979,460 control chromosomes in the GnomAD database, including 5,581 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.095 (691 hom., cov: 32)
  • Exomes 𝑓: 0.11 (4890 hom.)
• Consequence: TIMM23 ENST00000580018.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.314

Genes affected

TIMM23 (HGNC:17312): (translocase of inner mitochondrial membrane 23) The protein encoded by this gene is part of a complex located in the inner mitochondrial membrane that mediates the transport of transit peptide-containing proteins across the membrane. Multiple transcript variants, one protein-coding and others not protein-coding, have been found for this gene. [provided by RefSeq, Jul 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.109 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TIMM23	NM_006327.4	c.515-735C>T		intron_variant		ENST00000580018.4	NP_006318.1
TIMM23	NR_073029.2	n.758C>T		non_coding_transcript_exon_variant	7/8
TIMM23	NR_073030.2	n.592-735C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TIMM23	ENST00000580018.4	c.515-735C>T		intron_variant		1	NM_006327.4	ENSP00000464522	P1

Frequencies

GnomAD3 genomes AF: 0.0954 AC: 14487 AN: 151910 Hom.: 692 Cov.: 32

Gnomad AFR AF: 0.0755

Gnomad AMI AF: 0.152

Gnomad AMR AF: 0.0894

Gnomad ASJ AF: 0.0805

Gnomad EAS AF: 0.0819

Gnomad SAS AF: 0.0773

Gnomad FIN AF: 0.0925

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.0979

GnomAD4 exome AF: 0.107 AC: 88411 AN: 827434 Hom.: 4890 Cov.: 20 AF XY: 0.107 AC XY: 40877 AN XY: 382276

Gnomad4 AFR exome AF: 0.0734

Gnomad4 AMR exome AF: 0.0806

Gnomad4 ASJ exome AF: 0.0868

Gnomad4 EAS exome AF: 0.0702

Gnomad4 SAS exome AF: 0.0781

Gnomad4 FIN exome AF: 0.106

Gnomad4 NFE exome AF: 0.109

Gnomad4 OTH exome AF: 0.100

GnomAD4 genome AF: 0.0953 AC: 14485 AN: 152026 Hom.: 691 Cov.: 32 AF XY: 0.0935 AC XY: 6948 AN XY: 74324

Gnomad4 AFR AF: 0.0754

Gnomad4 AMR AF: 0.0893

Gnomad4 ASJ AF: 0.0805

Gnomad4 EAS AF: 0.0817

Gnomad4 SAS AF: 0.0769

Gnomad4 FIN AF: 0.0925

Gnomad4 NFE AF: 0.111

Gnomad4 OTH AF: 0.0964

Alfa AF: 0.108 Hom.: 1714

Bravo AF: 0.0941

Asia WGS AF: 0.0860 AC: 302 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.0
DANN	Benign	0.43

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs7085433; hg19: chr10-51593354;