Variant 9-137279140-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_017723.3(TOR4A):c.451G>C(p.Asp151His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000081 in 1,580,160 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000085 ( 0 hom. )

Consequence

TOR4A
NM_017723.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.23

Variant links:

Genes affected

TOR4A (HGNC:25981): (torsin family 4 member A) Predicted to enable ATP binding activity. Predicted to be located in extracellular region and platelet alpha granule lumen. Predicted to be active in endoplasmic reticulum lumen and nuclear envelope. [provided by Alliance of Genome Resources, Apr 2022]

TOR4A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.42391026).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TOR4A	NM_017723.3 linkuse as main transcript	c.451G>C	p.Asp151His	missense_variant	2/2	ENST00000357503.3	NP_060193.2	Q9NXH8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TOR4A	ENST00000357503.3 linkuse as main transcript	c.451G>C	p.Asp151His	missense_variant	2/2	2	NM_017723.3	ENSP00000350102.2		Q9NXH8

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000160

AC:

AN:

187700

Hom.:

AF XY:

0.00000980

AC XY:

AN XY:

102010

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000381

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000854

AC:

122

AN:

1427928

Hom.:

Cov.:

AF XY:

0.0000791

AC XY:

AN XY:

707606

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000110

Gnomad4 OTH exome

AF:

0.0000338

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152232

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000847

Hom.:

Bravo

AF:

0.0000567

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000228

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000251

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 28, 2022

The c.451G>C (p.D151H) alteration is located in exon 2 (coding exon 1) of the TOR4A gene. This alteration results from a G to C substitution at nucleotide position 451, causing the aspartic acid (D) at amino acid position 151 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.42

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.45

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.13

Eigen

Uncertain

0.48

Eigen_PC

Uncertain

0.42

FATHMM_MKL

Uncertain

0.86

LIST_S2

Uncertain

0.87

M_CAP

Pathogenic

0.31

MetaRNN

Benign

0.42

MetaSVM

Benign

-0.77

MutationAssessor

Benign

2.0

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.85

PROVEAN

Uncertain

-3.2

REVEL

Benign

0.20

Sift

Uncertain

0.0070

Sift4G

Uncertain

0.010

Polyphen

1.0

Vest4

0.22

MVP

0.32

MPC

2.4

ClinPred

0.75

GERP RS

3.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.38

gMVP

0.85

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