Variant 20-63740383-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_020062.4(SLC2A4RG):c.133T>A(p.Ser45Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000107 in 1,228,406 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000094 ( 0 hom. )

Consequence

SLC2A4RG
NM_020062.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.410

Variant links:

Genes affected

SLC2A4RG (HGNC:15930): (SLC2A4 regulator) The protein encoded by this gene is a nuclear transcription factor involved in the activation of the solute carrier family 2 member 4 gene. The encoded protein interacts with another transcription factor, myocyte enhancer factor 2, to activate transcription of this gene. [provided by RefSeq, Jul 2008]

SLC2A4RG links:

ENSG00000273047 (HGNC:):

ENSG00000273047 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.010084093).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC2A4RG	NM_020062.4 linkuse as main transcript	c.133T>A	p.Ser45Thr	missense_variant	2/8	ENST00000266077.5	NP_064446.2	Q9NR83-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC2A4RG	ENST00000266077.5 linkuse as main transcript	c.133T>A	p.Ser45Thr	missense_variant	2/8	1	NM_020062.4	ENSP00000266077.2		Q9NR83-1
ENSG00000273047	ENST00000467211.1 linkuse as main transcript	c.235T>A	p.Ser79Thr	missense_variant	2/2	3		ENSP00000477118.1		V9GYV3

Frequencies

GnomAD3 genomes

AF:

0.000197

AC:

AN:

151912

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:

0.00218

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00172

AC:

AN:

1744

Hom.:

AF XY:

0.00264

AC XY:

AN XY:

1136

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:

0.00277

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000938

AC:

101

AN:

1076386

Hom.:

Cov.:

AF XY:

0.000102

AC XY:

AN XY:

508756

show subpopulations

Gnomad4 AFR exome

AF:

0.0000441

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:

0.00248

Gnomad4 NFE exome

AF:

0.0000447

Gnomad4 OTH exome

AF:

0.0000694

GnomAD4 genome

AF:

0.000197

AC:

AN:

152020

Hom.:

Cov.:

AF XY:

0.000229

AC XY:

AN XY:

74314

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:

0.00218

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000318

Hom.:

Bravo

AF:

0.0000604

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

Sep 26, 2023

The c.133T>A (p.S45T) alteration is located in exon 2 (coding exon 2) of the SLC2A4RG gene. This alteration results from a T to A substitution at nucleotide position 133, causing the serine (S) at amino acid position 45 to be replaced by a threonine (T). 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

0.077

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.67

CADD

Benign

4.5

DANN

Benign

0.81

DEOGEN2

Benign

0.073

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.019

LIST_S2

Benign

0.25

M_CAP

Benign

0.050

MetaRNN

Benign

0.010

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-0.53

REVEL

Benign

0.017

Sift

Benign

0.15

Sift4G

Benign

0.27

Polyphen

0.023

Vest4

0.096

MVP

0.067

MPC

0.055

ClinPred

0.026

GERP RS

1.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.049

gMVP

0.094

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