20-4869923-G-C

Variant names:

• chr20-4869923-G-C
• rs762763708
• NM_005116.6:c.1233C>G

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP7 BS2

The NM_005116.6(SLC23A2):​c.1233C>G​(p.Pro411Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000136 in 1,175,658 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P411P) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: SLC23A2 NM_005116.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.143
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.013).
• BP7: Synonymous conserved (PhyloP=0.143 with no splicing effect.
• BS2: High AC in GnomAdExome4 at 16 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005116.6. 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
	SLC23A2	NM_005116.6	MANE Select	c.1233C>G	p.Pro411Pro	synonymous	Exon 12 of 17	NP_005107.4
	SLC23A2	NM_203327.2		c.1233C>G	p.Pro411Pro	synonymous	Exon 12 of 17	NP_976072.1	Q9UGH3-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC23A2	ENST00000338244.6	TSL:1 MANE Select	c.1233C>G	p.Pro411Pro	synonymous	Exon 12 of 17	ENSP00000344322.1	Q9UGH3-1
	SLC23A2	ENST00000379333.5	TSL:1	c.1233C>G	p.Pro411Pro	synonymous	Exon 12 of 17	ENSP00000368637.1	Q9UGH3-1
	SLC23A2	ENST00000468355.5	TSL:1	n.1599C>G		non_coding_transcript_exon	Exon 12 of 12

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00000519 AC: 1 AN: 192512 AF XY: 0.00000955

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000424

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000136 AC: 16 AN: 1175658 Hom.: 0 Cov.: 32 AF XY: 0.0000154 AC XY: 9 AN XY: 586256

African (AFR) AF: 0.0000373 AC: 1 AN: 26816

American (AMR) AF: 0.0000282 AC: 1 AN: 35418

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20324

East Asian (EAS) AF: 0.0000314 AC: 1 AN: 31800

South Asian (SAS) AF: 0.00 AC: 0 AN: 69434

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45666

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4830

European-Non Finnish (NFE) AF: 0.0000134 AC: 12 AN: 893308

Other (OTH) AF: 0.0000208 AC: 1 AN: 48062

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	6.7
DANN	Benign	0.63
PhyloP100		0.14
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

Other links and lift over

dbSNP: rs762763708; hg19: chr20-4850569;