rs3813628

Variant names:

• chr1-161226376-A-C
• rs3813628
• NM_032174.6:c.-114A>C

Your query was ambiguous. Multiple possible variants found:

• chr1-161226376-A-C
• chr1-161226376-A-T

Variant summary

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

The NM_032174.6(TOMM40L):​c.-114A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.338 in 869,156 control chromosomes in the GnomAD database, including 52,557 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 0.29 (7165 hom., cov: 27)
  • Exomes 𝑓: 0.35 (45392 hom.)
• Consequence: TOMM40L NM_032174.6 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.90
• Publications: 16 publications found

Genes affected

TOMM40L (HGNC:25756): (translocase of outer mitochondrial membrane 40 like) Predicted to enable protein transmembrane transporter activity. Predicted to be involved in protein import into mitochondrial matrix. Part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.518 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TOMM40L	NM_032174.6	c.-114A>C		5_prime_UTR_variant	Exon 2 of 10	ENST00000367988.8	NP_115550.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TOMM40L	ENST00000367988.8	c.-114A>C		5_prime_UTR_variant	Exon 2 of 10	2	NM_032174.6	ENSP00000356967.3

Frequencies

GnomAD3 genomes AF: 0.288 AC: 43297 AN: 150096 Hom.: 7165 Cov.: 27

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.320

Gnomad AMR AF: 0.356

Gnomad ASJ AF: 0.312

Gnomad EAS AF: 0.535

Gnomad SAS AF: 0.314

Gnomad FIN AF: 0.319

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.347

Gnomad OTH AF: 0.308

GnomAD4 exome AF: 0.349 AC: 250592 AN: 718940 Hom.: 45392 Cov.: 10 AF XY: 0.347 AC XY: 127073 AN XY: 366192

African (AFR) AF: 0.117 AC: 2060 AN: 17566

American (AMR) AF: 0.397 AC: 9248 AN: 23318

Ashkenazi Jewish (ASJ) AF: 0.326 AC: 5274 AN: 16178

East Asian (EAS) AF: 0.535 AC: 17192 AN: 32116

South Asian (SAS) AF: 0.318 AC: 17266 AN: 54312

European-Finnish (FIN) AF: 0.315 AC: 12318 AN: 39150

Middle Eastern (MID) AF: 0.324 AC: 828 AN: 2558

European-Non Finnish (NFE) AF: 0.350 AC: 174607 AN: 499184

Other (OTH) AF: 0.341 AC: 11799 AN: 34558

GnomAD4 genome AF: 0.288 AC: 43304 AN: 150216 Hom.: 7165 Cov.: 27 AF XY: 0.289 AC XY: 21206 AN XY: 73272

African (AFR) AF: 0.122 AC: 4969 AN: 40860

American (AMR) AF: 0.357 AC: 5386 AN: 15098

Ashkenazi Jewish (ASJ) AF: 0.312 AC: 1078 AN: 3460

East Asian (EAS) AF: 0.535 AC: 2661 AN: 4978

South Asian (SAS) AF: 0.313 AC: 1473 AN: 4710

European-Finnish (FIN) AF: 0.319 AC: 3290 AN: 10318

Middle Eastern (MID) AF: 0.276 AC: 81 AN: 294

European-Non Finnish (NFE) AF: 0.347 AC: 23438 AN: 67508

Other (OTH) AF: 0.306 AC: 639 AN: 2086

Alfa AF: 0.332 Hom.: 25337

Bravo AF: 0.286

Asia WGS AF: 0.434 AC: 1505 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	18
DANN	Benign	0.89
PhyloP100		1.9
PromoterAI		-0.016	Neutral
Mutation Taster		=300/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: rs3813628; hg19: chr1-161196166; COSMIC: COSV107457372; COSMIC: COSV107457372;