rs33954397

Variant names:

• chr22-32110156-C-T
• rs33954397
• NM_000343.4:c.1938C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_000343.4(SLC5A1):​c.1938C>T​(p.Asn646Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0657 in 1,613,880 control chromosomes in the GnomAD database, including 3,950 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.045 (211 hom., cov: 32)
  • Exomes 𝑓: 0.068 (3739 hom.)
• Consequence: SLC5A1 NM_000343.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.739
• Publications: 8 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: Orphanet, PanelApp Australia, Ambry Genetics, Labcorp Genetics (formerly Invitae)

LOC105373000 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.28).
• BP6: Variant 22-32110156-C-T is Benign according to our data. Variant chr22-32110156-C-T is described in ClinVar as Benign. ClinVar VariationId is 341267.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.739 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0689 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC5A1	NM_000343.4	MANE Select	c.1938C>T	p.Asn646Asn	synonymous	Exon 15 of 15	NP_000334.1
	SLC5A1	NM_001256314.2		c.1557C>T	p.Asn519Asn	synonymous	Exon 14 of 14	NP_001243243.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC5A1	ENST00000266088.9	TSL:1 MANE Select	c.1938C>T	p.Asn646Asn	synonymous	Exon 15 of 15	ENSP00000266088.4
	SLC5A1	ENST00000543737.2	TSL:2	c.1557C>T	p.Asn519Asn	synonymous	Exon 14 of 14	ENSP00000444898.1

Frequencies

GnomAD3 genomes AF: 0.0450 AC: 6853 AN: 152132 Hom.: 212 Cov.: 32

Gnomad AFR AF: 0.0123

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.0343

Gnomad ASJ AF: 0.0412

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.0377

Gnomad FIN AF: 0.0560

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0706

Gnomad OTH AF: 0.0369

GnomAD2 exomes AF: 0.0485 AC: 12205 AN: 251404 AF XY: 0.0496

Gnomad AFR exome AF: 0.0115

Gnomad AMR exome AF: 0.0291

Gnomad ASJ exome AF: 0.0382

Gnomad EAS exome AF: 0.00125

Gnomad FIN exome AF: 0.0517

Gnomad NFE exome AF: 0.0705

Gnomad OTH exome AF: 0.0454

GnomAD4 exome AF: 0.0679 AC: 99172 AN: 1461630 Hom.: 3739 Cov.: 32 AF XY: 0.0670 AC XY: 48751 AN XY: 727126

African (AFR) AF: 0.00995 AC: 333 AN: 33478

American (AMR) AF: 0.0318 AC: 1423 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.0408 AC: 1066 AN: 26134

East Asian (EAS) AF: 0.00186 AC: 74 AN: 39698

South Asian (SAS) AF: 0.0423 AC: 3649 AN: 86256

European-Finnish (FIN) AF: 0.0565 AC: 3019 AN: 53418

Middle Eastern (MID) AF: 0.0316 AC: 182 AN: 5762

European-Non Finnish (NFE) AF: 0.0773 AC: 85914 AN: 1111778

Other (OTH) AF: 0.0582 AC: 3512 AN: 60392

GnomAD4 genome AF: 0.0450 AC: 6854 AN: 152250 Hom.: 211 Cov.: 32 AF XY: 0.0435 AC XY: 3236 AN XY: 74448

African (AFR) AF: 0.0123 AC: 511 AN: 41540

American (AMR) AF: 0.0346 AC: 529 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0412 AC: 143 AN: 3472

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5188

South Asian (SAS) AF: 0.0381 AC: 184 AN: 4830

European-Finnish (FIN) AF: 0.0560 AC: 593 AN: 10592

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0706 AC: 4799 AN: 68010

Other (OTH) AF: 0.0365 AC: 77 AN: 2110

Alfa AF: 0.0599 Hom.: 131

Bravo AF: 0.0428

Asia WGS AF: 0.0200 AC: 71 AN: 3478

EpiCase AF: 0.0603

EpiControl AF: 0.0660

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Congenital glucose-galactose malabsorption (2)
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.28
CADD	Benign	5.4
DANN	Benign	0.68
PhyloP100		0.74
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: rs33954397; hg19: chr22-32506143; COSMIC: COSV56683033;