Variant chr22-35317938-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBS1BS2

The NM_005488.3(TOM1):c.114C>T(p.Asp38=) variant causes a synonymous change. The variant allele was found at a frequency of 0.00261 in 1,614,132 control chromosomes in the GnomAD database, including 101 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.014 ( 47 hom., cov: 32)

Exomes 𝑓: 0.0014 ( 54 hom. )

Consequence

TOM1
NM_005488.3 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 6.17

Variant links:

Genes affected

TOM1 (HGNC:11982): (target of myb1 membrane trafficking protein) This gene was identified as a target of the v-myb oncogene. The encoded protein shares its N-terminal domain in common with proteins associated with vesicular trafficking at the endosome. It is recruited to the endosomes by its interaction with endofin. Several alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2008]

TOM1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.28).

BP6

Variant 22-35317938-C-T is Benign according to our data. Variant chr22-35317938-C-T is described in ClinVar as [Benign]. Clinvar id is 778918.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0142 (2159/152278) while in subpopulation AFR AF= 0.0494 (2054/41550). AF 95% confidence interval is 0.0477. There are 47 homozygotes in gnomad4. There are 1004 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 2159 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TOM1	NM_005488.3 linkuse as main transcript	c.114C>T	p.Asp38=	synonymous_variant	2/15	ENST00000449058.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TOM1	ENST00000449058.7 linkuse as main transcript	c.114C>T	p.Asp38=	synonymous_variant	2/15	1	NM_005488.3	P3	O60784-1

Frequencies

GnomAD3 genomes

AF:

0.0141

AC:

2153

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0494

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00491

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.0105

GnomAD3 exomes

AF:

0.00366

AC:

920

AN:

251482

Hom.:

AF XY:

0.00259

AC XY:

352

AN XY:

135912

show subpopulations

Gnomad AFR exome

AF:

0.0498

Gnomad AMR exome

AF:

0.00237

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000132

Gnomad OTH exome

AF:

0.00195

GnomAD4 exome

AF:

0.00141

AC:

2058

AN:

1461854

Hom.:

Cov.:

AF XY:

0.00126

AC XY:

913

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.0485

Gnomad4 AMR exome

AF:

0.00239

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000696

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000953

Gnomad4 OTH exome

AF:

0.00341

GnomAD4 genome

AF:

0.0142

AC:

2159

AN:

152278

Hom.:

Cov.:

AF XY:

0.0135

AC XY:

1004

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.0494

Gnomad4 AMR

AF:

0.00490

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.0104

Alfa

AF:

0.00652

Hom.:

Bravo

AF:

0.0159

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000296

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Mar 01, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.28

CADD

Benign

DANN

Benign

0.93

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over