rs2293370

Variant names:

• chr3-119501087-G-A
• rs2293370
• NM_016589.4:c.360+227G>A

Your query was ambiguous. Multiple possible variants found:

• chr3-119501087-G-A
• chr3-119501087-G-C
• chr3-119501087-G-T

Variant summary

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

The NM_016589.4(TIMMDC1):​c.360+227G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 152,190 control chromosomes in the GnomAD database, including 2,715 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 0.19 (2715 hom., cov: 32)
• Consequence: TIMMDC1 NM_016589.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.459
• Publications: 78 publications found

Genes affected

TIMMDC1 (HGNC:1321): (translocase of inner mitochondrial membrane domain containing 1) Located in mitochondrion and nucleoplasm. Implicated in nuclear type mitochondrial complex I deficiency 31. [provided by Alliance of Genome Resources, Apr 2022]

TIMMDC1 Gene-Disease associations (from GenCC):

• mitochondrial complex I deficiency, nuclear type 31

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Illumina, Labcorp Genetics (formerly Invitae)
• mitochondrial complex I deficiency

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Leigh syndrome

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.317 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TIMMDC1	NM_016589.4	c.360+227G>A		intron_variant	Intron 2 of 6	ENST00000494664.6	NP_057673.2
TIMMDC1	NM_001438040.1	c.194+2160G>A		intron_variant	Intron 1 of 2		NP_001424969.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TIMMDC1	ENST00000494664.6	c.360+227G>A		intron_variant	Intron 2 of 6	1	NM_016589.4	ENSP00000418803.1

Frequencies

GnomAD3 genomes AF: 0.185 AC: 28158 AN: 152072 Hom.: 2716 Cov.: 32

Gnomad AFR AF: 0.201

Gnomad AMI AF: 0.212

Gnomad AMR AF: 0.137

Gnomad ASJ AF: 0.151

Gnomad EAS AF: 0.330

Gnomad SAS AF: 0.191

Gnomad FIN AF: 0.119

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.187

Gnomad OTH AF: 0.186

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

GnomAD4 genome AF: 0.185 AC: 28165 AN: 152190 Hom.: 2715 Cov.: 32 AF XY: 0.181 AC XY: 13486 AN XY: 74412

African (AFR) AF: 0.201 AC: 8328 AN: 41514

American (AMR) AF: 0.136 AC: 2087 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.151 AC: 523 AN: 3472

East Asian (EAS) AF: 0.330 AC: 1712 AN: 5184

South Asian (SAS) AF: 0.190 AC: 918 AN: 4824

European-Finnish (FIN) AF: 0.119 AC: 1264 AN: 10586

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.187 AC: 12684 AN: 67994

Other (OTH) AF: 0.187 AC: 396 AN: 2116

Alfa AF: 0.189 Hom.: 9607

Bravo AF: 0.186

Asia WGS AF: 0.241 AC: 837 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.16
DANN	Benign	0.67
PhyloP100		-0.46
Mutation Taster		=100/0	polymorphism (auto)

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: rs2293370; hg19: chr3-119219934;