3-119498942-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_016589.4(TIMMDC1):c.194+15G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00431 in 1,613,194 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0034 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0044 (18 hom.)
• Consequence: TIMMDC1 NM_016589.4 intron
• Scores: Splicing: ADA: 0.0006994
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.70

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 3-119498942-G-T is Benign according to our data. Variant chr3-119498942-G-T is described in ClinVar as [Benign]. Clinvar id is 1592296.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00343 (522/152298) while in subpopulation NFE AF= 0.00529 (360/68026). AF 95% confidence interval is 0.00484. There are 0 homozygotes in gnomad4. There are 247 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TIMMDC1	NM_016589.4	c.194+15G>T		intron_variant		ENST00000494664.6
TIMMDC1	XM_017006556.2	c.194+15G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TIMMDC1	ENST00000494664.6	c.194+15G>T		intron_variant		1	NM_016589.4	P1

Frequencies

GnomAD3 genomes AF: 0.00343 AC: 522 AN: 152180 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00439

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00565

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00529

Gnomad OTH AF: 0.000955

GnomAD3 exomes AF: 0.00327 AC: 816 AN: 249472 Hom.: 3 AF XY: 0.00321 AC XY: 434 AN XY: 135302

Gnomad AFR exome AF: 0.000644

Gnomad AMR exome AF: 0.00130

Gnomad ASJ exome AF: 0.000499

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000785

Gnomad FIN exome AF: 0.00560

Gnomad NFE exome AF: 0.00523

Gnomad OTH exome AF: 0.00347

GnomAD4 exome AF: 0.00440 AC: 6426 AN: 1460896 Hom.: 18 Cov.: 31 AF XY: 0.00433 AC XY: 3149 AN XY: 726666

Gnomad4 AFR exome AF: 0.000718

Gnomad4 AMR exome AF: 0.00139

Gnomad4 ASJ exome AF: 0.000191

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000580

Gnomad4 FIN exome AF: 0.00506

Gnomad4 NFE exome AF: 0.00524

Gnomad4 OTH exome AF: 0.00320

GnomAD4 genome AF: 0.00343 AC: 522 AN: 152298 Hom.: 0 Cov.: 32 AF XY: 0.00332 AC XY: 247 AN XY: 74472

Gnomad4 AFR AF: 0.000722

Gnomad4 AMR AF: 0.00438

Gnomad4 ASJ AF: 0.000576

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00565

Gnomad4 NFE AF: 0.00529

Gnomad4 OTH AF: 0.000945

Alfa AF: 0.00273 Hom.: 0

Bravo AF: 0.00312

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 29, 2024

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	14
Dann	Benign	0.55

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00070
SpliceAI score (max)		0.090		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: rs200200314; hg19: chr3-119217789;