Variant 7-100223919-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NR_028040.1(CASTOR3P):n.623T>C variant causes a non coding transcript exon change. The variant allele was found at a frequency of 0.0000347 in 1,613,900 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000034 ( 0 hom. )

Consequence

CASTOR3P
NR_028040.1 non_coding_transcript_exon

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.10

Variant links:

Genes affected

CASTOR3P (HGNC:29954): (CASTOR family member 3, pseudogene) Predicted to be involved in cellular response to L-arginine and negative regulation of TORC1 signaling. Predicted to be active in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

CASTOR3P links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.859

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons
CASTOR3P	NR_028040.1 linkuse as main transcript	n.623T>C	non_coding_transcript_exon_variant	3/6
CASTOR3P	NR_028038.2 linkuse as main transcript	n.596T>C	non_coding_transcript_exon_variant	3/7
CASTOR3P	NR_028039.1 linkuse as main transcript	n.623T>C	non_coding_transcript_exon_variant	3/8
CASTOR3P	NR_166147.1 linkuse as main transcript	n.596T>C	non_coding_transcript_exon_variant	3/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CASTOR3P	ENST00000647868.1 linkuse as main transcript	n.374T>C		non_coding_transcript_exon_variant	3/5
CASTOR3P	ENST00000649671.1 linkuse as main transcript	n.609T>C		non_coding_transcript_exon_variant	3/5

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000882

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000642

AC:

AN:

249378

Hom.:

AF XY:

0.0000961

AC XY:

AN XY:

135302

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:

0.0000654

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000115

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.0000335

AC:

AN:

1461694

Hom.:

Cov.:

AF XY:

0.0000440

AC XY:

AN XY:

727154

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000378

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152206

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000882

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.0000900

Hom.:

Bravo

AF:

0.0000227

ExAC

AF:

0.0000826

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.000178

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 29, 2024

The c.374T>C (p.V125A) alteration is located in exon 3 (coding exon 3) of the GATS gene. This alteration results from a T to C substitution at nucleotide position 374, causing the valine (V) at amino acid position 125 to be replaced by an alanine (A). 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

0.34

BayesDel_addAF

Benign

0.0022

BayesDel_noAF

Uncertain

-0.010

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.32

Eigen

Uncertain

0.30

Eigen_PC

Benign

0.077

FATHMM_MKL

Uncertain

0.85

LIST_S2

Uncertain

0.96

M_CAP

Benign

0.0022

MetaRNN

Pathogenic

0.86

MetaSVM

Benign

-0.39

MutationTaster

Benign

0.91

PROVEAN

Uncertain

-3.7

REVEL

Benign

0.28

Sift

Uncertain

0.0020

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.86

MutPred

0.67

Loss of sheet (P = 7e-04);

MVP

0.30

MPC

1.4

ClinPred

0.54

GERP RS

1.1

Varity_R

0.26

gMVP

0.91

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