rs71352238

Variant names:

• chr19-44891079-T-C
• rs71352238
• ENST00000927372.1:c.-105T>C

Variant summary

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

The ENST00000927372.1(TOMM40):​c.-105T>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 0.113 in 217,226 control chromosomes in the GnomAD database, including 1,713 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 0.11 (1080 hom., cov: 33)
  • Exomes 𝑓: 0.13 (633 hom.)
• Consequence: TOMM40 ENST00000927372.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.711
• Publications: 65 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]

LNCOB1 (HGNC:56209):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.141 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000927372.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TOMM40	NM_001128917.2	MANE Select	c.-337T>C		upstream_gene	N/A	NP_001122389.1	O96008-1
	TOMM40	NM_001128916.2		c.-245T>C		upstream_gene	N/A	NP_001122388.1	O96008-1
	TOMM40	NM_006114.3		c.-242T>C		upstream_gene	N/A	NP_006105.1	O96008-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TOMM40	ENST00000927372.1		c.-105T>C		5_prime_UTR	Exon 1 of 7	ENSP00000597431.1
	TOMM40	ENST00000947713.1		c.-10+84T>C		intron	N/A	ENSP00000617772.1
	TOMM40	ENST00000589253.1	TSL:3	c.-9-328T>C		intron	N/A	ENSP00000465611.1	K7EKG6

Frequencies

GnomAD3 genomes AF: 0.105 AC: 16002 AN: 152160 Hom.: 1073 Cov.: 33

Gnomad AFR AF: 0.0257

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.0924

Gnomad ASJ AF: 0.114

Gnomad EAS AF: 0.109

Gnomad SAS AF: 0.120

Gnomad FIN AF: 0.184

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.143

Gnomad OTH AF: 0.0813

GnomAD4 exome AF: 0.130 AC: 8474 AN: 64946 Hom.: 633 AF XY: 0.131 AC XY: 4304 AN XY: 32950

African (AFR) AF: 0.0209 AC: 46 AN: 2200

American (AMR) AF: 0.0815 AC: 143 AN: 1754

Ashkenazi Jewish (ASJ) AF: 0.100 AC: 257 AN: 2558

East Asian (EAS) AF: 0.136 AC: 705 AN: 5176

South Asian (SAS) AF: 0.111 AC: 75 AN: 676

European-Finnish (FIN) AF: 0.178 AC: 963 AN: 5424

Middle Eastern (MID) AF: 0.0381 AC: 16 AN: 420

European-Non Finnish (NFE) AF: 0.138 AC: 5811 AN: 42182

Other (OTH) AF: 0.101 AC: 458 AN: 4556

GnomAD4 genome AF: 0.105 AC: 16024 AN: 152280 Hom.: 1080 Cov.: 33 AF XY: 0.108 AC XY: 8069 AN XY: 74458

African (AFR) AF: 0.0257 AC: 1067 AN: 41592

American (AMR) AF: 0.0934 AC: 1428 AN: 15292

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

East Asian (EAS) AF: 0.109 AC: 563 AN: 5174

South Asian (SAS) AF: 0.119 AC: 576 AN: 4834

European-Finnish (FIN) AF: 0.184 AC: 1948 AN: 10600

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.143 AC: 9716 AN: 68000

Other (OTH) AF: 0.0870 AC: 184 AN: 2114

Alfa AF: 0.116 Hom.: 1255

Bravo AF: 0.0922

Asia WGS AF: 0.165 AC: 572 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	5.1
DANN	Benign	0.23
PhyloP100		-0.71
PromoterAI		0.042	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs71352238; hg19: chr19-45394336;