19-44892362-A-G

Variant names:

• chr19-44892362-A-G
• rs2075650
• NM_001128917.2:c.275-31A>G

Variant summary

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

The NM_001128917.2(TOMM40):​c.275-31A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 1,608,116 control chromosomes in the GnomAD database, including 16,065 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 0.13 (1342 hom., cov: 32)
  • Exomes 𝑓: 0.14 (14723 hom.)
• Consequence: TOMM40 NM_001128917.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.03
• Publications: 526 publications found

Genes affected

TOMM40 (HGNC:18001): (translocase of outer mitochondrial membrane 40) The protein encoded by this gene is localized in the outer membrane of the mitochondria. It is the channel-forming subunit of the translocase of the mitochondrial outer membrane (TOM) complex that is essential for import of protein precursors into mitochondria. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Aug 2015]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.136 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TOMM40	NM_001128917.2	c.275-31A>G		intron_variant	Intron 1 of 8	ENST00000426677.7	NP_001122389.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TOMM40	ENST00000426677.7	c.275-31A>G		intron_variant	Intron 1 of 8	1	NM_001128917.2	ENSP00000410339.1

Frequencies

GnomAD3 genomes AF: 0.132 AC: 20043 AN: 151888 Hom.: 1333 Cov.: 32

Gnomad AFR AF: 0.129

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.105

Gnomad ASJ AF: 0.114

Gnomad EAS AF: 0.108

Gnomad SAS AF: 0.122

Gnomad FIN AF: 0.172

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.138

Gnomad OTH AF: 0.0970

GnomAD2 exomes AF: 0.129 AC: 32485 AN: 251370 AF XY: 0.129

Gnomad AFR exome AF: 0.124

Gnomad AMR exome AF: 0.0978

Gnomad ASJ exome AF: 0.104

Gnomad EAS exome AF: 0.0865

Gnomad FIN exome AF: 0.182

Gnomad NFE exome AF: 0.143

Gnomad OTH exome AF: 0.122

GnomAD4 exome AF: 0.141 AC: 205242 AN: 1456110 Hom.: 14723 Cov.: 30 AF XY: 0.141 AC XY: 101870 AN XY: 724748

African (AFR) AF: 0.124 AC: 4135 AN: 33352

American (AMR) AF: 0.0984 AC: 4397 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.111 AC: 2892 AN: 26092

East Asian (EAS) AF: 0.129 AC: 5119 AN: 39678

South Asian (SAS) AF: 0.118 AC: 10185 AN: 86142

European-Finnish (FIN) AF: 0.175 AC: 9351 AN: 53404

Middle Eastern (MID) AF: 0.0580 AC: 333 AN: 5746

European-Non Finnish (NFE) AF: 0.146 AC: 161294 AN: 1106810

Other (OTH) AF: 0.125 AC: 7536 AN: 60188

GnomAD4 genome AF: 0.132 AC: 20086 AN: 152006 Hom.: 1342 Cov.: 32 AF XY: 0.133 AC XY: 9904 AN XY: 74288

African (AFR) AF: 0.129 AC: 5363 AN: 41454

American (AMR) AF: 0.106 AC: 1612 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.114 AC: 397 AN: 3468

East Asian (EAS) AF: 0.108 AC: 560 AN: 5170

South Asian (SAS) AF: 0.121 AC: 581 AN: 4818

European-Finnish (FIN) AF: 0.172 AC: 1820 AN: 10564

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.138 AC: 9387 AN: 67952

Other (OTH) AF: 0.103 AC: 216 AN: 2104

Alfa AF: 0.134 Hom.: 5232

Bravo AF: 0.124

Asia WGS AF: 0.172 AC: 598 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.5
DANN	Benign	0.78
PhyloP100		-1.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs2075650; hg19: chr19-45395619; COSMIC: COSV52977687; COSMIC: COSV52977687;