22-32043366-A-G

Position:

• chr22-32043366-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_000343.4(SLC5A1):​c.85A>G​(p.Ile29Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,860 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SLC5A1 NM_000343.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.68

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.33126006).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC5A1	NM_000343.4	c.85A>G	p.Ile29Val	missense_variant	1/15	ENST00000266088.9	NP_000334.1
SLC5A1	XM_011530331.2	c.85A>G	p.Ile29Val	missense_variant	1/12		XP_011528633.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC5A1	ENST00000266088.9	c.85A>G	p.Ile29Val	missense_variant	1/15	1	NM_000343.4	ENSP00000266088.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000797 AC: 2 AN: 250792 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135616

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461860 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727224

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Congenital glucose-galactose malabsorption Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Apr 15, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.017
Eigen_PC	Benign	0.067
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.81	T
M_CAP	Uncertain	0.091	D
MetaRNN	Benign	0.33	T
MetaSVM	Uncertain	0.0051	D
MutationAssessor	Uncertain	2.7	M
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-0.78	N
REVEL	Uncertain	0.54
Sift	Benign	0.039	D
Sift4G	Uncertain	0.055	T
Polyphen		0.025	B
Vest4		0.48
MutPred		0.64		Loss of glycosylation at S30 (P = 0.1376);
MVP		0.78
MPC		0.41
ClinPred		0.70	D
GERP RS		4.8
Varity_R		0.18
gMVP		0.37

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs753830321; hg19: chr22-32439353;