NM_020062.4:c.681-3C>G

Variant names:

• chr20-63742333-C-G
• rs1046617
• NM_020062.4:c.681-3C>G

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_020062.4(SLC2A4RG):​c.681-3C>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,454,742 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SLC2A4RG NM_020062.4 splice_region, intron
• Scores: Splicing: ADA: 0.9998
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.30
• 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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF. Scorers claiming Uncertain: max_spliceai. No scorers claiming Benign.

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.681-3C>G		splice_region intron	N/A	NP_064446.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC2A4RG	ENST00000266077.5	TSL:1 MANE Select	c.681-3C>G		splice_region intron	N/A	ENSP00000266077.2	Q9NR83-1
	SLC2A4RG	ENST00000493772.5	TSL:1	n.330-3C>G		splice_region intron	N/A
	SLC2A4RG	ENST00000872204.1		c.707C>G	p.Ala236Gly	missense	Exon 6 of 8	ENSP00000542263.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1454742 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 722784

African (AFR) AF: 0.00 AC: 0 AN: 33348

American (AMR) AF: 0.00 AC: 0 AN: 44412

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25830

East Asian (EAS) AF: 0.00 AC: 0 AN: 39546

South Asian (SAS) AF: 0.0000117 AC: 1 AN: 85644

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51990

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5622

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1108320

Other (OTH) AF: 0.00 AC: 0 AN: 60030

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	21
DANN	Benign	0.91
PhyloP100		1.3
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		3.0

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	1.0
dbscSNV1_RF	Pathogenic	0.95
SpliceAI score (max)		0.39		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.22		Position offset: 10
DS_AL_spliceai		0.39		Position offset: 3

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1046617; hg19: chr20-62373686;