Genetic Variant NM_005116.6:c.858C>T (chr20-4874663-G-A) – ACMG Classification: Benign (-15 pts)

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The NM_005116.6(SLC23A2):c.858C>T(p.Tyr286Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00993 in 1,611,212 control chromosomes in the GnomAD database, including 102 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.011 ( 11 hom., cov: 32)

Exomes 𝑓: 0.0098 ( 91 hom. )

Consequence

SLC23A2
NM_005116.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.00

Publications

5 publications found

Variant links:

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 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -15 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.15).

BP6

Variant 20-4874663-G-A is Benign according to our data. Variant chr20-4874663-G-A is described in ClinVar as Benign. ClinVar VariationId is 777298.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=2.01 with no splicing effect.

BS2

High AC in GnomAd4 at 1639 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.858C>T	p.Tyr286Tyr	synonymous	Exon 10 of 17	NP_005107.4
	SLC23A2	NM_203327.2		c.858C>T	p.Tyr286Tyr	synonymous	Exon 10 of 17	NP_976072.1	Q9UGH3-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC23A2	ENST00000338244.6	TSL:1 MANE Select	c.858C>T	p.Tyr286Tyr	synonymous	Exon 10 of 17	ENSP00000344322.1	Q9UGH3-1
SLC23A2	ENST00000379333.5	TSL:1	c.858C>T	p.Tyr286Tyr	synonymous	Exon 10 of 17	ENSP00000368637.1	Q9UGH3-1
SLC23A2	ENST00000468355.5	TSL:1	n.1224C>T		non_coding_transcript_exon	Exon 10 of 12

Frequencies

GnomAD3 genomes

AF:

0.0107

AC:

1633

AN:

152122

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0107

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0112

Gnomad ASJ

AF:

0.0182

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0174

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0109

Gnomad OTH

AF:

0.0144

GnomAD2 exomes

AF:

0.00941

AC:

2359

AN:

250636

AF XY:

0.00846

show subpopulations

Gnomad AFR exome

AF:

0.0130

Gnomad AMR exome

AF:

0.0111

Gnomad ASJ exome

AF:

0.0203

Gnomad EAS exome

AF:

0.000109

Gnomad FIN exome

AF:

0.0143

Gnomad NFE exome

AF:

0.00996

Gnomad OTH exome

AF:

0.0185

GnomAD4 exome

AF:

0.00985

AC:

14365

AN:

1458972

Hom.:

Cov.:

AF XY:

0.00947

AC XY:

6872

AN XY:

725924

show subpopulations

African (AFR)

AF:

0.0110

AC:

369

AN:

33414

American (AMR)

AF:

0.0114

AC:

505

AN:

44478

Ashkenazi Jewish (ASJ)

AF:

0.0191

AC:

499

AN:

26062

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39654

South Asian (SAS)

AF:

0.000395

AC:

AN:

86058

European-Finnish (FIN)

AF:

0.0141

AC:

751

AN:

53382

Middle Eastern (MID)

AF:

0.00867

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.0103

AC:

11428

AN:

1109896

Other (OTH)

AF:

0.0121

AC:

727

AN:

60264

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

631

1262

1893

2524

3155

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

436

872

1308

1744

2180

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0108

AC:

1639

AN:

152240

Hom.:

Cov.:

AF XY:

0.0108

AC XY:

802

AN XY:

74428

show subpopulations

African (AFR)

AF:

0.0108

AC:

447

AN:

41538

American (AMR)

AF:

0.0112

AC:

172

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0182

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.000415

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.0174

AC:

184

AN:

10590

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0108

AC:

738

AN:

68028

Other (OTH)

AF:

0.0142

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

170

254

339

424

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

110

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0109

Hom.:

Bravo

AF:

0.0110

Asia WGS

AF:

0.00289

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

(source)

DANN

Benign

0.23

PhyloP100

2.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=98/2

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over