9-137279257-C-A

Position:

• chr9-137279257-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_017723.3(TOR4A):​c.568C>A​(p.Leu190Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TOR4A NM_017723.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.647

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TOR4A	NM_017723.3	c.568C>A	p.Leu190Met	missense_variant	2/2	ENST00000357503.3	NP_060193.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TOR4A	ENST00000357503.3	c.568C>A	p.Leu190Met	missense_variant	2/2	2	NM_017723.3	ENSP00000350102	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1383050 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 681660

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 07, 2023

The c.568C>A (p.L190M) alteration is located in exon 2 (coding exon 1) of the TOR4A gene. This alteration results from a C to A substitution at nucleotide position 568, causing the leucine (L) at amino acid position 190 to be replaced by a methionine (M). 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	0.31
BayesDel_addAF	Benign	-0.047	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.023	T
Eigen	Uncertain	0.21
Eigen_PC	Benign	0.16
FATHMM_MKL	Benign	0.39	N
LIST_S2	Benign	0.47	T
M_CAP	Uncertain	0.28	D
MetaRNN	Uncertain	0.43	T
MetaSVM	Benign	-0.80	T
MutationAssessor	Benign	1.6	L
MutationTaster	Benign	1.0	D
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.26
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.019	D
Polyphen		1.0	D
Vest4		0.43
MutPred		0.69		Gain of disorder (P = 0.1606);
MVP		0.32
MPC		2.2
ClinPred		0.85	D
GERP RS		2.7
Varity_R		0.25
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-140173709;