chr22-32043287-C-T

Position:

• chr22-32043287-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_000343.4(SLC5A1):​c.6C>T​(p.Asp2=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0114 in 1,614,004 control chromosomes in the GnomAD database, including 263 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.012 (37 hom., cov: 32)
  • Exomes 𝑓: 0.011 (226 hom.)
• Consequence: SLC5A1 NM_000343.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 1.51

Genes affected

SLC5A1 (HGNC:11036): (solute carrier family 5 member 1) This gene encodes a member of the sodium-dependent glucose transporter (SGLT) family. The encoded integral membrane protein is the primary mediator of dietary glucose and galactose uptake from the intestinal lumen. Mutations in this gene have been associated with glucose-galactose malabsorption. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2012]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant 22-32043287-C-T is Benign according to our data. Variant chr22-32043287-C-T is described in ClinVar as [Benign]. Clinvar id is 341234.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.51 with no splicing effect.
• BA1: GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0748 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC5A1	NM_000343.4	c.6C>T	p.Asp2=	synonymous_variant	1/15	ENST00000266088.9
SLC5A1	XM_011530331.2	c.6C>T	p.Asp2=	synonymous_variant	1/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC5A1	ENST00000266088.9	c.6C>T	p.Asp2=	synonymous_variant	1/15	1	NM_000343.4	P1

Frequencies

GnomAD3 genomes AF: 0.0117 AC: 1775 AN: 152238 Hom.: 33 Cov.: 32

Gnomad AFR AF: 0.00292

Gnomad AMI AF: 0.0208

Gnomad AMR AF: 0.0502

Gnomad ASJ AF: 0.0308

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00559

Gnomad FIN AF: 0.00424

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00939

Gnomad OTH AF: 0.0215

GnomAD3 exomes AF: 0.0178 AC: 4470 AN: 250554 Hom.: 137 AF XY: 0.0152 AC XY: 2066 AN XY: 135530

Gnomad AFR exome AF: 0.00284

Gnomad AMR exome AF: 0.0796

Gnomad ASJ exome AF: 0.0300

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.00434

Gnomad FIN exome AF: 0.00362

Gnomad NFE exome AF: 0.00944

Gnomad OTH exome AF: 0.0149

GnomAD4 exome AF: 0.0114 AC: 16647 AN: 1461648 Hom.: 226 Cov.: 32 AF XY: 0.0109 AC XY: 7893 AN XY: 727146

Gnomad4 AFR exome AF: 0.00194

Gnomad4 AMR exome AF: 0.0769

Gnomad4 ASJ exome AF: 0.0284

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.00464

Gnomad4 FIN exome AF: 0.00387

Gnomad4 NFE exome AF: 0.00997

Gnomad4 OTH exome AF: 0.0113

GnomAD4 genome AF: 0.0117 AC: 1782 AN: 152356 Hom.: 37 Cov.: 32 AF XY: 0.0114 AC XY: 847 AN XY: 74494

Gnomad4 AFR AF: 0.00291

Gnomad4 AMR AF: 0.0508

Gnomad4 ASJ AF: 0.0308

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00539

Gnomad4 FIN AF: 0.00424

Gnomad4 NFE AF: 0.00938

Gnomad4 OTH AF: 0.0208

Alfa AF: 0.0114 Hom.: 9

Bravo AF: 0.0154

Asia WGS AF: 0.00808 AC: 29 AN: 3478

EpiCase AF: 0.00867

EpiControl AF: 0.00836

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Congenital glucose-galactose malabsorption Benign:3

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Fulgent Genetics, Fulgent Genetics	Oct 11, 2021	- -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	9.3
DANN	Benign	0.97

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: rs33973317; hg19: chr22-32439274;