chr19-44899791-C-CTTTTTTTT

Variant names:

• chr19-44899791-C-CTTTTTTTT
• rs10524523
• NM_001128917.2:c.644-911_644-904dupTTTTTTTT

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001128917.2(TOMM40):​c.644-911_644-904dupTTTTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0010 (10 hom., cov: 0)
• Consequence: TOMM40 NM_001128917.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.01
• Publications: 124 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: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAd4 at 95 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001128917.2. 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.644-911_644-904dupTTTTTTTT		intron	N/A	NP_001122389.1	O96008-1
	TOMM40	NM_001128916.2		c.644-911_644-904dupTTTTTTTT		intron	N/A	NP_001122388.1	O96008-1
	TOMM40	NM_006114.3		c.644-911_644-904dupTTTTTTTT		intron	N/A	NP_006105.1	O96008-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TOMM40	ENST00000426677.7	TSL:1 MANE Select	c.644-939_644-938insTTTTTTTT		intron	N/A	ENSP00000410339.1	O96008-1
	TOMM40	ENST00000252487.9	TSL:1	c.644-939_644-938insTTTTTTTT		intron	N/A	ENSP00000252487.4	O96008-1
	TOMM40	ENST00000405636.6	TSL:1	c.644-939_644-938insTTTTTTTT		intron	N/A	ENSP00000385184.2	O96008-1

Frequencies

GnomAD3 genomes AF: 0.00104 AC: 95 AN: 90954 Hom.: 10 Cov.: 0

Gnomad AFR AF: 0.000297

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00147

Gnomad ASJ AF: 0.00250

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000459

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00154

Gnomad OTH AF: 0.000814

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

GnomAD4 genome AF: 0.00104 AC: 95 AN: 90962 Hom.: 10 Cov.: 0 AF XY: 0.00113 AC XY: 47 AN XY: 41712

African (AFR) AF: 0.000297 AC: 8 AN: 26938

American (AMR) AF: 0.00147 AC: 10 AN: 6794

Ashkenazi Jewish (ASJ) AF: 0.00250 AC: 6 AN: 2396

East Asian (EAS) AF: 0.00 AC: 0 AN: 2394

South Asian (SAS) AF: 0.000460 AC: 1 AN: 2172

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 3312

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 126

European-Non Finnish (NFE) AF: 0.00154 AC: 69 AN: 44942

Other (OTH) AF: 0.000808 AC: 1 AN: 1238

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-2.0

Splicing

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

Other links and lift over

dbSNP: rs10524523; hg19: chr19-45403048;