22-32110117-G-A

Variant names:

• chr22-32110117-G-A
• rs33943816
• NM_000343.4:c.1899G>A
• SLC5A1 p.Thr633Thr

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.1899G>A​(p.Thr633Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.057 in 1,613,924 control chromosomes in the GnomAD database, including 2,932 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.042 (180 hom., cov: 32)
  • Exomes 𝑓: 0.058 (2752 hom.)
• Consequence: SLC5A1 NM_000343.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -1.37
• 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: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae), PanelApp Australia

LOC105373000 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP6: Variant 22-32110117-G-A is Benign according to our data. Variant chr22-32110117-G-A is described in ClinVar as Benign. ClinVar VariationId is 341265.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.37 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0587 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.1899G>A	p.Thr633Thr	synonymous	Exon 15 of 15	NP_000334.1	P13866-1
	SLC5A1	NM_001256314.2		c.1518G>A	p.Thr506Thr	synonymous	Exon 14 of 14	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.1899G>A	p.Thr633Thr	synonymous	Exon 15 of 15	ENSP00000266088.4	P13866-1
	SLC5A1	ENST00000878506.1		c.1791G>A	p.Thr597Thr	synonymous	Exon 14 of 14	ENSP00000548565.1
	SLC5A1	ENST00000543737.2	TSL:2	c.1518G>A	p.Thr506Thr	synonymous	Exon 14 of 14	ENSP00000444898.1	P13866-2

Frequencies

GnomAD3 genomes AF: 0.0424 AC: 6454 AN: 152134 Hom.: 178 Cov.: 32

Gnomad AFR AF: 0.0118

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.0568

Gnomad ASJ AF: 0.0914

Gnomad EAS AF: 0.0204

Gnomad SAS AF: 0.0443

Gnomad FIN AF: 0.0203

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0602

Gnomad OTH AF: 0.0598

GnomAD2 exomes AF: 0.0461 AC: 11587 AN: 251432 AF XY: 0.0478

Gnomad AFR exome AF: 0.00960

Gnomad AMR exome AF: 0.0371

Gnomad ASJ exome AF: 0.0994

Gnomad EAS exome AF: 0.0208

Gnomad FIN exome AF: 0.0192

Gnomad NFE exome AF: 0.0581

Gnomad OTH exome AF: 0.0593

GnomAD4 exome AF: 0.0585 AC: 85463 AN: 1461672 Hom.: 2752 Cov.: 32 AF XY: 0.0582 AC XY: 42348 AN XY: 727136

African (AFR) AF: 0.0115 AC: 386 AN: 33478

American (AMR) AF: 0.0380 AC: 1701 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.0998 AC: 2609 AN: 26136

East Asian (EAS) AF: 0.0147 AC: 584 AN: 39700

South Asian (SAS) AF: 0.0451 AC: 3893 AN: 86256

European-Finnish (FIN) AF: 0.0207 AC: 1105 AN: 53420

Middle Eastern (MID) AF: 0.0744 AC: 429 AN: 5768

European-Non Finnish (NFE) AF: 0.0638 AC: 70971 AN: 1111812

Other (OTH) AF: 0.0627 AC: 3785 AN: 60386

GnomAD4 genome AF: 0.0424 AC: 6459 AN: 152252 Hom.: 180 Cov.: 32 AF XY: 0.0408 AC XY: 3036 AN XY: 74444

African (AFR) AF: 0.0118 AC: 490 AN: 41550

American (AMR) AF: 0.0567 AC: 867 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0914 AC: 317 AN: 3470

East Asian (EAS) AF: 0.0206 AC: 107 AN: 5188

South Asian (SAS) AF: 0.0439 AC: 212 AN: 4828

European-Finnish (FIN) AF: 0.0203 AC: 215 AN: 10600

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0602 AC: 4095 AN: 68000

Other (OTH) AF: 0.0620 AC: 131 AN: 2114

Alfa AF: 0.0448 Hom.: 151

Bravo AF: 0.0435

Asia WGS AF: 0.0630 AC: 219 AN: 3478

EpiCase AF: 0.0606

EpiControl AF: 0.0626

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	0.48
DANN	Benign	0.76
PhyloP100		-1.4
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs33943816;

hg19: chr22-32506104;

COSMIC: COSV56689723;