5-139378681-G-C

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_005847.5(SLC23A1):c.1077C>G(p.Gly359=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0011 in 1,604,672 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0015 (6 hom., cov: 32)
  • Exomes 𝑓: 0.0011 (25 hom.)
• Consequence: SLC23A1 NM_005847.5 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.407

Genes affected

SLC23A1 (HGNC:10974): (solute carrier family 23 member 1) 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 transporters. The encoded protein is active in bulk vitamin C transport involving epithelial surfaces. Previously, this gene had an official symbol of SLC23A2. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2008]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BP6: Variant 5-139378681-G-C is Benign according to our data. Variant chr5-139378681-G-C is described in ClinVar as [Benign]. Clinvar id is 709227.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.407 with no splicing effect.
• BS2: High Homozygotes in GnomAd at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC23A1	NM_005847.5	c.1077C>G	p.Gly359=	synonymous_variant	10/15	ENST00000348729.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC23A1	ENST00000348729.8	c.1077C>G	p.Gly359=	synonymous_variant	10/15	1	NM_005847.5	P1
SLC23A1	ENST00000353963.7	c.1089C>G	p.Gly363=	synonymous_variant	10/15	1
SLC23A1	ENST00000504513.1	c.318C>G	p.Gly106=	synonymous_variant	4/4	5

Frequencies

GnomAD3 genomes AF: 0.00148 AC: 225 AN: 152158 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00137

Gnomad ASJ AF: 0.0510

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000265

Gnomad OTH AF: 0.00335

GnomAD3 exomes AF: 0.00209 AC: 489 AN: 233500 Hom.: 10 AF XY: 0.00204 AC XY: 257 AN XY: 126234

Gnomad AFR exome AF: 0.000140

Gnomad AMR exome AF: 0.000546

Gnomad ASJ exome AF: 0.0398

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000560

Gnomad OTH exome AF: 0.00465

GnomAD4 exome AF: 0.00106 AC: 1536 AN: 1452396 Hom.: 25 Cov.: 32 AF XY: 0.00109 AC XY: 790 AN XY: 721678

Gnomad4 AFR exome AF: 0.0000900

Gnomad4 AMR exome AF: 0.000780

Gnomad4 ASJ exome AF: 0.0422

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000205

Gnomad4 OTH exome AF: 0.00301

GnomAD4 genome AF: 0.00148 AC: 225 AN: 152276 Hom.: 6 Cov.: 32 AF XY: 0.00152 AC XY: 113 AN XY: 74444

Gnomad4 AFR AF: 0.0000481

Gnomad4 AMR AF: 0.00137

Gnomad4 ASJ AF: 0.0510

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000265

Gnomad4 OTH AF: 0.00332

Alfa AF: 0.00460 Hom.: 3

Bravo AF: 0.00147

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Apr 11, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
Cadd	Benign	3.3
Dann	Benign	0.67

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: rs145899167; hg19: chr5-138714370;