1-48228927-C-G

Variant names:

• chr1-48228927-C-G
• rs200586919
• NM_001011547.3:c.312C>G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Moderate BP6 BP7 BS2

The NM_001011547.3(SLC5A9):​c.312C>G​(p.Gly104Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00161 in 1,613,442 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.00094 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0017 (2 hom.)
• Consequence: SLC5A9 NM_001011547.3 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.188

Genes affected

SLC5A9 (HGNC:22146): (solute carrier family 5 member 9) Predicted to enable glucose:sodium symporter activity. Predicted to be involved in sodium ion transport. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000272491 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).
• BP6: Variant 1-48228927-C-G is Benign according to our data. Variant chr1-48228927-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 3047851.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-0.188 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC5A9	NM_001011547.3	c.312C>G	p.Gly104Gly	synonymous_variant	Exon 3 of 14	ENST00000438567.7	NP_001011547.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC5A9	ENST00000438567.7	c.312C>G	p.Gly104Gly	synonymous_variant	Exon 3 of 14	1	NM_001011547.3	ENSP00000401730.2

Frequencies

GnomAD3 genomes AF: 0.000940 AC: 143 AN: 152176 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000314

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.000393

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00103

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00168

Gnomad OTH AF: 0.000956

GnomAD3 exomes AF: 0.000979 AC: 245 AN: 250328 Hom.: 0 AF XY: 0.000998 AC XY: 135 AN XY: 135292

Gnomad AFR exome AF: 0.000431

Gnomad AMR exome AF: 0.000607

Gnomad ASJ exome AF: 0.0000992

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000457

Gnomad FIN exome AF: 0.0000481

Gnomad NFE exome AF: 0.00170

Gnomad OTH exome AF: 0.00131

GnomAD4 exome AF: 0.00168 AC: 2454 AN: 1461148 Hom.: 2 Cov.: 31 AF XY: 0.00163 AC XY: 1188 AN XY: 726856

Gnomad4 AFR exome AF: 0.000269

Gnomad4 AMR exome AF: 0.000581

Gnomad4 ASJ exome AF: 0.000115

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000603

Gnomad4 FIN exome AF: 0.000152

Gnomad4 NFE exome AF: 0.00204

Gnomad4 OTH exome AF: 0.00147

GnomAD4 genome AF: 0.000939 AC: 143 AN: 152294 Hom.: 0 Cov.: 32 AF XY: 0.000913 AC XY: 68 AN XY: 74462

Gnomad4 AFR AF: 0.000313

Gnomad4 AMR AF: 0.000392

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00103

Gnomad4 FIN AF: 0.000188

Gnomad4 NFE AF: 0.00168

Gnomad4 OTH AF: 0.000946

Alfa AF: 0.00102 Hom.: 0

Bravo AF: 0.000884

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00256

EpiControl AF: 0.00178

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

SLC5A9-related disorder Benign:1

Jan 05, 2024

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	14
DANN	Benign	0.69
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs200586919; hg19: chr1-48694599;