rs5998233

Variant names:

• chr22-32086334-T-G
• rs5998233
• NM_000343.4:c.1129+7T>G

Your query was ambiguous. Multiple possible variants found:

• chr22-32086334-T-G
• chr22-32086334-T-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000343.4(SLC5A1):​c.1129+7T>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.391 in 1,588,556 control chromosomes in the GnomAD database, including 131,733 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.48 (20763 hom., cov: 31)
  • Exomes 𝑓: 0.38 (110970 hom.)
• Consequence: SLC5A1 NM_000343.4 splice_region, intron
• Scores: Splicing: ADA: 0.00002167
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.979
• Publications: 6 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 22-32086334-T-G is Benign according to our data. Variant chr22-32086334-T-G is described in ClinVar as Benign. ClinVar VariationId is 341249.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.808 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.1129+7T>G		splice_region intron	N/A	NP_000334.1	P13866-1
	SLC5A1	NM_001256314.2		c.748+7T>G		splice_region intron	N/A	NP_001243243.1	P13866-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC5A1	ENST00000266088.9	TSL:1 MANE Select	c.1129+7T>G		splice_region intron	N/A	ENSP00000266088.4	P13866-1
	SLC5A1	ENST00000878506.1		c.1021+1299T>G		intron	N/A	ENSP00000548565.1
	SLC5A1	ENST00000543737.2	TSL:2	c.748+7T>G		splice_region intron	N/A	ENSP00000444898.1	P13866-2

Frequencies

GnomAD3 genomes AF: 0.476 AC: 72305 AN: 151838 Hom.: 20709 Cov.: 31

Gnomad AFR AF: 0.815

Gnomad AMI AF: 0.398

Gnomad AMR AF: 0.346

Gnomad ASJ AF: 0.396

Gnomad EAS AF: 0.157

Gnomad SAS AF: 0.374

Gnomad FIN AF: 0.278

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.369

Gnomad OTH AF: 0.425

GnomAD2 exomes AF: 0.362 AC: 90985 AN: 251372 AF XY: 0.359

Gnomad AFR exome AF: 0.827

Gnomad AMR exome AF: 0.274

Gnomad ASJ exome AF: 0.386

Gnomad EAS exome AF: 0.164

Gnomad FIN exome AF: 0.274

Gnomad NFE exome AF: 0.367

Gnomad OTH exome AF: 0.344

GnomAD4 exome AF: 0.382 AC: 548795 AN: 1436600 Hom.: 110970 Cov.: 25 AF XY: 0.380 AC XY: 272334 AN XY: 716406

African (AFR) AF: 0.839 AC: 27712 AN: 33038

American (AMR) AF: 0.278 AC: 12441 AN: 44694

Ashkenazi Jewish (ASJ) AF: 0.384 AC: 9967 AN: 25950

East Asian (EAS) AF: 0.151 AC: 5972 AN: 39544

South Asian (SAS) AF: 0.378 AC: 32432 AN: 85842

European-Finnish (FIN) AF: 0.282 AC: 15057 AN: 53318

Middle Eastern (MID) AF: 0.378 AC: 2159 AN: 5718

European-Non Finnish (NFE) AF: 0.385 AC: 419676 AN: 1089012

Other (OTH) AF: 0.393 AC: 23379 AN: 59484

GnomAD4 genome AF: 0.477 AC: 72421 AN: 151956 Hom.: 20763 Cov.: 31 AF XY: 0.466 AC XY: 34580 AN XY: 74278

African (AFR) AF: 0.815 AC: 33761 AN: 41410

American (AMR) AF: 0.346 AC: 5278 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.396 AC: 1373 AN: 3470

East Asian (EAS) AF: 0.157 AC: 813 AN: 5172

South Asian (SAS) AF: 0.375 AC: 1805 AN: 4818

European-Finnish (FIN) AF: 0.278 AC: 2944 AN: 10574

Middle Eastern (MID) AF: 0.388 AC: 114 AN: 294

European-Non Finnish (NFE) AF: 0.369 AC: 25072 AN: 67938

Other (OTH) AF: 0.426 AC: 898 AN: 2110

Alfa AF: 0.415 Hom.: 6730

Bravo AF: 0.494

Asia WGS AF: 0.327 AC: 1137 AN: 3478

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)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.84
DANN	Benign	0.65
PhyloP100		-0.98
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000022
dbscSNV1_RF	Benign	0.0
SpliceAI score (max)		0.020		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: rs5998233; hg19: chr22-32482321; COSMIC: COSV56688825; COSMIC: COSV56688825;