22-32043287-C-T

Variant names:

• chr22-32043287-C-T
• rs33973317
• NM_000343.4:c.6C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_000343.4(SLC5A1):​c.6C>T​(p.Asp2Asp) 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
• Publications: 7 publications found

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]

SLC5A1 Gene-Disease associations (from GenCC):

• glucose-galactose malabsorption

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, PanelApp Australia, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000343.4. 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
	SLC5A1	NM_000343.4	MANE Select	c.6C>T	p.Asp2Asp	synonymous	Exon 1 of 15	NP_000334.1	P13866-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC5A1	ENST00000266088.9	TSL:1 MANE Select	c.6C>T	p.Asp2Asp	synonymous	Exon 1 of 15	ENSP00000266088.4	P13866-1
	SLC5A1	ENST00000878506.1		c.6C>T	p.Asp2Asp	synonymous	Exon 1 of 14	ENSP00000548565.1

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

GnomAD2 exomes AF: 0.0178 AC: 4470 AN: 250554 AF XY: 0.0152

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 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

African (AFR) AF: 0.00194 AC: 65 AN: 33480

American (AMR) AF: 0.0769 AC: 3438 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.0284 AC: 742 AN: 26136

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39698

South Asian (SAS) AF: 0.00464 AC: 400 AN: 86256

European-Finnish (FIN) AF: 0.00387 AC: 206 AN: 53228

Middle Eastern (MID) AF: 0.00503 AC: 29 AN: 5768

European-Non Finnish (NFE) AF: 0.00997 AC: 11085 AN: 1111996

Other (OTH) AF: 0.0113 AC: 680 AN: 60384

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

African (AFR) AF: 0.00291 AC: 121 AN: 41596

American (AMR) AF: 0.0508 AC: 778 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0308 AC: 107 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00539 AC: 26 AN: 4828

European-Finnish (FIN) AF: 0.00424 AC: 45 AN: 10622

Middle Eastern (MID) AF: 0.0137 AC: 4 AN: 292

European-Non Finnish (NFE) AF: 0.00938 AC: 638 AN: 68030

Other (OTH) AF: 0.0208 AC: 44 AN: 2112

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	Congenital glucose-galactose malabsorption (3)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	9.3
DANN	Benign	0.97
PhyloP100		1.5
PromoterAI		-0.075	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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: rs33973317; hg19: chr22-32439274;