20-63741455-G-A

Position:

• chr20-63741455-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_020062.4(SLC2A4RG):​c.367G>A​(p.Ala123Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,080 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: not found (cov: 34)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SLC2A4RG NM_020062.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.341

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 (HGNC:):

ACMG classification

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=0.059048057).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC2A4RG	NM_020062.4	c.367G>A	p.Ala123Thr	missense_variant	3/8	ENST00000266077.5	NP_064446.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC2A4RG	ENST00000266077.5	c.367G>A	p.Ala123Thr	missense_variant	3/8	1	NM_020062.4	ENSP00000266077.2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461080 Hom.: 0 Cov.: 48 AF XY: 0.00 AC XY: 0 AN XY: 726870

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

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

Mar 26, 2024

The c.367G>A (p.A123T) alteration is located in exon 3 (coding exon 3) of the SLC2A4RG gene. This alteration results from a G to A substitution at nucleotide position 367, causing the alanine (A) at amino acid position 123 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	0.069
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	8.2
DANN	Uncertain	0.99
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.66
FATHMM_MKL	Benign	0.33	N
LIST_S2	Benign	0.60	T
M_CAP	Benign	0.0073	T
MetaRNN	Benign	0.059	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.021
Sift	Benign	0.083	T
Sift4G	Uncertain	0.045	D
Polyphen		0.11	B
Vest4		0.058
MutPred		0.33		Gain of glycosylation at A123 (P = 0.0138);
MVP		0.048
MPC		0.10
ClinPred		0.090	T
GERP RS		0.43
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.056
gMVP		0.21

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: chr20-62372808;