20-63739976-T-A

Variant names:

• chr20-63739976-T-A
• rs1015743280
• NM_020062.4:c.64T>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_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. 15/22 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.28
• Publications: 0 publications found

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]

ENSG00000273047 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.05802217).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020062.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC2A4RG	NM_020062.4	MANE Select	c.64T>A	p.Trp22Arg	missense	Exon 1 of 8	NP_064446.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC2A4RG	ENST00000266077.5	TSL:1 MANE Select	c.64T>A	p.Trp22Arg	missense	Exon 1 of 8	ENSP00000266077.2	Q9NR83-1
	ENSG00000273047	ENST00000467211.1	TSL:3	c.229-401T>A		intron	N/A	ENSP00000477118.1	V9GYV3
	SLC2A4RG	ENST00000946584.1		c.64T>A	p.Trp22Arg	missense	Exon 1 of 8	ENSP00000616643.1

Frequencies

GnomAD3 genomes AF: 0.000138 AC: 20 AN: 144916 Hom.: 0 Cov.: 31

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.: 1 Cov.: 31 AF XY: 0.000223 AC XY: 86 AN XY: 385428

African (AFR) AF: 0.000190 AC: 3 AN: 15794

American (AMR) AF: 0.00 AC: 0 AN: 1024

Ashkenazi Jewish (ASJ) AF: 0.000387 AC: 2 AN: 5172

East Asian (EAS) AF: 0.00 AC: 0 AN: 3644

South Asian (SAS) AF: 0.00 AC: 0 AN: 17038

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 322

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1630

European-Non Finnish (NFE) AF: 0.000245 AC: 187 AN: 762518

Other (OTH) AF: 0.0000366 AC: 1 AN: 27350

GnomAD4 genome AF: 0.000138 AC: 20 AN: 144916 Hom.: 0 Cov.: 31 AF XY: 0.000142 AC XY: 10 AN XY: 70514

African (AFR) AF: 0.0000990 AC: 4 AN: 40386

American (AMR) AF: 0.00 AC: 0 AN: 14680

Ashkenazi Jewish (ASJ) AF: 0.000592 AC: 2 AN: 3378

East Asian (EAS) AF: 0.00 AC: 0 AN: 4938

South Asian (SAS) AF: 0.00 AC: 0 AN: 4764

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8202

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 308

European-Non Finnish (NFE) AF: 0.000214 AC: 14 AN: 65352

Other (OTH) AF: 0.00 AC: 0 AN: 2004

Alfa AF: 0.000142 Hom.: 0

Bravo AF: 0.000121

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	12
DANN	Benign	0.79
DEOGEN2	Benign	0.093	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0077	N
LIST_S2	Benign	0.17	T
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.058	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		-2.3
PrimateAI	Pathogenic	0.79	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.020
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.0010	B
Vest4		0.086
MutPred		0.25		Gain of methylation at W22 (P = 0.0078)
MVP		0.061
MPC		0.10
ClinPred		0.14	T
GERP RS		-1.7
PromoterAI		0.037	Neutral
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.8
Varity_R		0.20
gMVP		0.14
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs1015743280; hg19: chr20-62371329;