10-46001360-A-G

Variant names:

• chr10-46001360-A-G
• rs7350420
• NM_006327.4:c.515-1843A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006327.4(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 NM_006327.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0930
• Publications: 20 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006327.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TIMM23	NM_006327.4	MANE Select	c.515-1843A>G		intron	N/A	NP_006318.1
	TIMM23	NR_073029.2		n.651-1001A>G		intron	N/A
	TIMM23	NR_073030.2		n.592-1843A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TIMM23	ENST00000580018.4	TSL:1 MANE Select	c.515-1843A>G		intron	N/A	ENSP00000464522.3

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

African (AFR) AF: 0.0663 AC: 2753 AN: 41528

American (AMR) AF: 0.372 AC: 5678 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.276 AC: 957 AN: 3470

East Asian (EAS) AF: 0.386 AC: 1988 AN: 5152

South Asian (SAS) AF: 0.199 AC: 958 AN: 4824

European-Finnish (FIN) AF: 0.375 AC: 3951 AN: 10524

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.331 AC: 22518 AN: 67960

Other (OTH) AF: 0.253 AC: 534 AN: 2108

Alfa AF: 0.307 Hom.: 24195

Bravo AF: 0.261

Asia WGS AF: 0.245 AC: 851 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	2.3
DANN	Benign	0.69
PhyloP100		0.093

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

Other links and lift over

dbSNP: rs7350420; hg19: chr10-51594462;