Variant 9-137279009-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.320G>C(p.Arg107Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000275 in 1,453,428 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: not found (cov: 33)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

TOR4A
NM_017723.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.210

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:

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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=0.28723675).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TOR4A	NM_017723.3 linkuse as main transcript	c.320G>C	p.Arg107Pro	missense_variant	2/2	ENST00000357503.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TOR4A	ENST00000357503.3 linkuse as main transcript	c.320G>C	p.Arg107Pro	missense_variant	2/2	2	NM_017723.3	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000441

AC:

AN:

226798

Hom.:

AF XY:

0.00000803

AC XY:

AN XY:

124554

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:

0.0000100

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000275

AC:

AN:

1453428

Hom.:

Cov.:

AF XY:

0.00000277

AC XY:

AN XY:

722590

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:

0.00000361

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Jan 31, 2024

The c.320G>C (p.R107P) 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 320, causing the arginine (R) at amino acid position 107 to be replaced by a proline (P). 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

Benign

0.28

BayesDel_addAF

Uncertain

0.046

BayesDel_noAF

Benign

-0.17

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.048

Eigen

Uncertain

0.24

Eigen_PC

Benign

0.13

FATHMM_MKL

Benign

0.29

LIST_S2

Benign

0.58

M_CAP

Pathogenic

0.36

MetaRNN

Benign

0.29

MetaSVM

Benign

-0.63

MutationAssessor

Uncertain

2.5

MutationTaster

Benign

0.89

PrimateAI

Uncertain

0.76

PROVEAN

Uncertain

-2.9

REVEL

Benign

0.22

Sift

Benign

0.036

Sift4G

Uncertain

0.057

Polyphen

1.0

Vest4

0.33

MutPred

0.32

Loss of MoRF binding (P = 0.0031);

MVP

0.34

MPC

2.1

ClinPred

0.95

GERP RS

3.7

Varity_R

0.52

gMVP

0.88

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