20-63740384-C-T

Variant names:

• chr20-63740384-C-T
• rs1379753904
• NM_020062.4:c.134C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020062.4(SLC2A4RG):​c.134C>T​(p.Ser45Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,076,398 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S45Y) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000019 (0 hom.)
• Consequence: SLC2A4RG NM_020062.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.618
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09164864).

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.134C>T	p.Ser45Phe	missense	Exon 2 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.134C>T	p.Ser45Phe	missense	Exon 2 of 8	ENSP00000266077.2	Q9NR83-1
	ENSG00000273047	ENST00000467211.1	TSL:3	c.236C>T	p.Ser79Phe	missense	Exon 2 of 2	ENSP00000477118.1	V9GYV3
	SLC2A4RG	ENST00000946584.1		c.191C>T	p.Ser64Phe	missense	Exon 2 of 8	ENSP00000616643.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000186 AC: 2 AN: 1076398 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 508766

African (AFR) AF: 0.00 AC: 0 AN: 22648

American (AMR) AF: 0.00 AC: 0 AN: 8190

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14080

East Asian (EAS) AF: 0.00 AC: 0 AN: 26148

South Asian (SAS) AF: 0.00 AC: 0 AN: 19684

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 22536

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2904

European-Non Finnish (NFE) AF: 0.00000218 AC: 2 AN: 916966

Other (OTH) AF: 0.00 AC: 0 AN: 43242

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

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	0.11
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	8.4
DANN	Benign	0.83
DEOGEN2	Benign	0.095	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.035	N
LIST_S2	Benign	0.41	T
M_CAP	Uncertain	0.16	D
MetaRNN	Benign	0.092	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
PhyloP100		-0.62
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.034
Sift	Uncertain	0.019	D
Sift4G	Uncertain	0.038	D
Polyphen		0.091	B
Vest4		0.11
MutPred		0.21		Loss of glycosylation at S45 (P = 0.0216)
MVP		0.095
MPC		0.063
ClinPred		0.075	T
GERP RS		2.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.046
gMVP		0.091
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1379753904; hg19: chr20-62371737; COSMIC: COSV99046184; COSMIC: COSV99046184;