NM_006327.4:c.515-735C>T

Variant names:

• chr10-46002468-C-T
• rs7085433
• NM_006327.4:c.515-735C>T

Variant summary

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

The NM_006327.4(TIMM23):​c.515-735C>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 NM_006327.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.314
• Publications: 31 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=-0.82).
• 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 rank	MANE	Protein	UniProt
TIMM23	NM_006327.4	c.515-735C>T		intron_variant	Intron 6 of 6	ENST00000580018.4	NP_006318.1
TIMM23	NR_073029.2	n.758C>T		non_coding_transcript_exon_variant	Exon 7 of 8
TIMM23	NR_073030.2	n.592-735C>T		intron_variant	Intron 5 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TIMM23	ENST00000580018.4	c.515-735C>T		intron_variant	Intron 6 of 6	1	NM_006327.4	ENSP00000464522.3

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

African (AFR) AF: 0.0734 AC: 1151 AN: 15672

American (AMR) AF: 0.0806 AC: 79 AN: 980

Ashkenazi Jewish (ASJ) AF: 0.0868 AC: 445 AN: 5128

East Asian (EAS) AF: 0.0702 AC: 253 AN: 3604

South Asian (SAS) AF: 0.0781 AC: 1277 AN: 16352

European-Finnish (FIN) AF: 0.106 AC: 29 AN: 274

Middle Eastern (MID) AF: 0.0892 AC: 144 AN: 1614

European-Non Finnish (NFE) AF: 0.109 AC: 82307 AN: 756672

Other (OTH) AF: 0.100 AC: 2726 AN: 27138

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

African (AFR) AF: 0.0754 AC: 3127 AN: 41454

American (AMR) AF: 0.0893 AC: 1364 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.0805 AC: 279 AN: 3464

East Asian (EAS) AF: 0.0817 AC: 422 AN: 5166

South Asian (SAS) AF: 0.0769 AC: 371 AN: 4822

European-Finnish (FIN) AF: 0.0925 AC: 977 AN: 10558

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.111 AC: 7577 AN: 67984

Other (OTH) AF: 0.0964 AC: 203 AN: 2106

Alfa AF: 0.106 Hom.: 3494

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
PhyloP100		-0.31

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

Other links and lift over

dbSNP: rs7085433; hg19: chr10-51593354;