chr10-46001360-A-G

Position:

• chr10-46001360-A-G

Variant summary

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

The ENST00000580018.4(TIMM23):​c.515-1843A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.261 in 152,040 control chromosomes in the GnomAD database, including 6,538 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 0.26 (6538 hom., cov: 32)
• Consequence: TIMM23 ENST00000580018.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0930

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=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.372 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TIMM23	NM_006327.4	c.515-1843A>G		intron_variant		ENST00000580018.4	NP_006318.1
TIMM23	NR_073029.2	n.651-1001A>G		intron_variant, non_coding_transcript_variant
TIMM23	NR_073030.2	n.592-1843A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TIMM23	ENST00000580018.4	c.515-1843A>G		intron_variant		1	NM_006327.4	ENSP00000464522	P1

Frequencies

GnomAD3 genomes AF: 0.261 AC: 39720 AN: 151922 Hom.: 6537 Cov.: 32

Gnomad AFR AF: 0.0666

Gnomad AMI AF: 0.360

Gnomad AMR AF: 0.371

Gnomad ASJ AF: 0.276

Gnomad EAS AF: 0.386

Gnomad SAS AF: 0.198

Gnomad FIN AF: 0.375

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.331

Gnomad OTH AF: 0.256

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

GnomAD4 genome AF: 0.261 AC: 39722 AN: 152040 Hom.: 6538 Cov.: 32 AF XY: 0.262 AC XY: 19477 AN XY: 74280

Gnomad4 AFR AF: 0.0663

Gnomad4 AMR AF: 0.372

Gnomad4 ASJ AF: 0.276

Gnomad4 EAS AF: 0.386

Gnomad4 SAS AF: 0.199

Gnomad4 FIN AF: 0.375

Gnomad4 NFE AF: 0.331

Gnomad4 OTH AF: 0.253

Alfa AF: 0.320 Hom.: 15119

Bravo AF: 0.261

Asia WGS AF: 0.245 AC: 851 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	2.3
DANN	Benign	0.69

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: rs7350420; hg19: chr10-51594462;