chr20-63741456-C-T

Position:

• chr20-63741456-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020062.4(SLC2A4RG):​c.368C>T​(p.Ala123Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,028 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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. A123D) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: SLC2A4RG NM_020062.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.170

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13480324).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC2A4RG	NM_020062.4	c.368C>T	p.Ala123Val	missense_variant	3/8	ENST00000266077.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC2A4RG	ENST00000266077.5	c.368C>T	p.Ala123Val	missense_variant	3/8	1	NM_020062.4	P1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD3 exomes AF: 0.00000801 AC: 2 AN: 249736 Hom.: 0 AF XY: 0.00000739 AC XY: 1 AN XY: 135278

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000890

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461028 Hom.: 0 Cov.: 49 AF XY: 0.00000275 AC XY: 2 AN XY: 726840

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

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: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

Alfa AF: 0.0000254 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	15
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.34
FATHMM_MKL	Benign	0.40	N
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	L
MutationTaster	Benign	0.99	N
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.034
Sift	Benign	0.10	T
Sift4G	Uncertain	0.0080	D
Polyphen		0.76	P
Vest4		0.074
MutPred		0.37		Gain of sheet (P = 0.039);
MVP		0.085
MPC		0.25
ClinPred		0.51	D
GERP RS		2.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.052
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

LitVar

Other links and lift over

dbSNP: rs375432430; hg19: chr20-62372809;