rs1110277

Positions:

• chr20-4874036-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_005116.6(SLC23A2):​c.1002T>C​(p.Asp334Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.349 in 1,613,582 control chromosomes in the GnomAD database, including 103,923 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.42 (15636 hom., cov: 32)
  • Exomes 𝑓: 0.34 (88287 hom.)
• Consequence: SLC23A2 NM_005116.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.844

Genes affected

SLC23A2 (HGNC:10973): (solute carrier family 23 member 2) The absorption of vitamin C into the body and its distribution to organs requires two sodium-dependent vitamin C transporters. This gene encodes one of the two required transporters and the encoded protein accounts for tissue-specific uptake of vitamin C. Previously, this gene had an official symbol of SLC23A1. [provided by RefSeq, Jul 2008]

SLC23A2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP7: Synonymous conserved (PhyloP=-0.844 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.67 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC23A2	NM_005116.6	c.1002T>C	p.Asp334Asp	synonymous_variant	11/17	ENST00000338244.6	NP_005107.4
SLC23A2	NM_203327.2	c.1002T>C	p.Asp334Asp	synonymous_variant	11/17		NP_976072.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC23A2	ENST00000338244.6	c.1002T>C	p.Asp334Asp	synonymous_variant	11/17	1	NM_005116.6	ENSP00000344322.1

Frequencies

GnomAD3 genomes AF: 0.424 AC: 64380 AN: 151972 Hom.: 15593 Cov.: 32

Gnomad AFR AF: 0.676

Gnomad AMI AF: 0.389

Gnomad AMR AF: 0.333

Gnomad ASJ AF: 0.290

Gnomad EAS AF: 0.244

Gnomad SAS AF: 0.379

Gnomad FIN AF: 0.309

Gnomad MID AF: 0.414

Gnomad NFE AF: 0.333

Gnomad OTH AF: 0.414

GnomAD3 exomes AF: 0.345 AC: 86623 AN: 251148 Hom.: 16324 AF XY: 0.342 AC XY: 46451 AN XY: 135720

Gnomad AFR exome AF: 0.684

Gnomad AMR exome AF: 0.296

Gnomad ASJ exome AF: 0.301

Gnomad EAS exome AF: 0.236

Gnomad SAS exome AF: 0.376

Gnomad FIN exome AF: 0.296

Gnomad NFE exome AF: 0.334

Gnomad OTH exome AF: 0.339

GnomAD4 exome AF: 0.341 AC: 498245 AN: 1461492 Hom.: 88287 Cov.: 35 AF XY: 0.341 AC XY: 247819 AN XY: 727054

Gnomad4 AFR exome AF: 0.690

Gnomad4 AMR exome AF: 0.302

Gnomad4 ASJ exome AF: 0.303

Gnomad4 EAS exome AF: 0.228

Gnomad4 SAS exome AF: 0.377

Gnomad4 FIN exome AF: 0.293

Gnomad4 NFE exome AF: 0.335

Gnomad4 OTH exome AF: 0.352

GnomAD4 genome AF: 0.424 AC: 64479 AN: 152090 Hom.: 15636 Cov.: 32 AF XY: 0.421 AC XY: 31278 AN XY: 74340

Gnomad4 AFR AF: 0.677

Gnomad4 AMR AF: 0.332

Gnomad4 ASJ AF: 0.290

Gnomad4 EAS AF: 0.244

Gnomad4 SAS AF: 0.381

Gnomad4 FIN AF: 0.309

Gnomad4 NFE AF: 0.333

Gnomad4 OTH AF: 0.411

Alfa AF: 0.350 Hom.: 22303

Bravo AF: 0.435

Asia WGS AF: 0.296 AC: 1032 AN: 3478

EpiCase AF: 0.341

EpiControl AF: 0.340

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.48
DANN	Benign	0.36
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

Publications

LitVar

Other links and lift over

dbSNP: rs1110277; hg19: chr20-4854682; COSMIC: COSV57774696; COSMIC: COSV57774696;