Variant 20-63739976-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.64T>A(p.Trp22Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000217 in 979,408 control chromosomes in the GnomAD database, including 1 homozygotes. 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 0.00014 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00023 ( 1 hom. )

Consequence

SLC2A4RG
NM_020062.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.28

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:

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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=0.05802217).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC2A4RG	NM_020062.4 linkuse as main transcript	c.64T>A	p.Trp22Arg	missense_variant	1/8	ENST00000266077.5	NP_064446.2	Q9NR83-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SLC2A4RG	ENST00000266077.5 linkuse as main transcript	c.64T>A	p.Trp22Arg	missense_variant	1/8	1	NM_020062.4	ENSP00000266077.2	Q9NR83-1
ENSG00000273047	ENST00000467211.1 linkuse as main transcript	c.229-401T>A		intron_variant		3		ENSP00000477118.1	V9GYV3
ENSG00000273047	ENST00000476221.1 linkuse as main transcript	n.425-401T>A		intron_variant		5

Frequencies

GnomAD3 genomes

AF:

0.000138

AC:

AN:

144916

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000990

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000592

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000214

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000231

AC:

193

AN:

834492

Hom.:

Cov.:

AF XY:

0.000223

AC XY:

AN XY:

385428

show subpopulations

Gnomad4 AFR exome

AF:

0.000190

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.000387

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000245

Gnomad4 OTH exome

AF:

0.0000366

GnomAD4 genome

AF:

0.000138

AC:

AN:

144916

Hom.:

Cov.:

AF XY:

0.000142

AC XY:

AN XY:

70514

show subpopulations

Gnomad4 AFR

AF:

0.0000990

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.000592

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000214

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.000121

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

Apr 11, 2023

The c.64T>A (p.W22R) alteration is located in exon 1 (coding exon 1) of the SLC2A4RG gene. This alteration results from a T to A substitution at nucleotide position 64, causing the tryptophan (W) at amino acid position 22 to be replaced by an arginine (R). 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

0.17

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.66

CADD

Benign

DANN

Benign

0.79

DEOGEN2

Benign

0.093

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0077

LIST_S2

Benign

0.17

M_CAP

Benign

0.031

MetaRNN

Benign

0.058

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PrimateAI

Pathogenic

0.79

PROVEAN

Benign

-1.6

REVEL

Benign

0.020

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.0010

Vest4

0.086

MutPred

0.25

Gain of methylation at W22 (P = 0.0078);

MVP

0.061

MPC

0.10

ClinPred

0.14

GERP RS

-1.7

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

2.8

Varity_R

0.20

gMVP

0.14

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