22-32091713-G-C

Variant names:

• chr22-32091713-G-C
• rs17683430
• NM_000343.4:c.1231G>C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM1 PM2 BP4

The NM_000343.4(SLC5A1):​c.1231G>C​(p.Ala411Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC5A1 NM_000343.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.30

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 3 ACMG points.

• PM1: In a disulfide_bond (size 256) in uniprot entity SC5A1_HUMAN there are 15 pathogenic changes around while only 0 benign (100%) in NM_000343.4
• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3144034).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC5A1	NM_000343.4	c.1231G>C	p.Ala411Pro	missense_variant	Exon 11 of 15	ENST00000266088.9	NP_000334.1
SLC5A1	NM_001256314.2	c.850G>C	p.Ala284Pro	missense_variant	Exon 10 of 14		NP_001243243.1
SLC5A1	XM_011530331.2	c.1231G>C	p.Ala411Pro	missense_variant	Exon 11 of 12		XP_011528633.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC5A1	ENST00000266088.9	c.1231G>C	p.Ala411Pro	missense_variant	Exon 11 of 15	1	NM_000343.4	ENSP00000266088.4
SLC5A1	ENST00000543737.2	c.850G>C	p.Ala284Pro	missense_variant	Exon 10 of 14	2		ENSP00000444898.1
SLC5A1	ENST00000477969.1	n.397G>C		non_coding_transcript_exon_variant	Exon 3 of 5	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.46
BayesDel_addAF	Benign	-0.021	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.072	T;.
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.095
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.65	T;T
M_CAP	Uncertain	0.13	D
MetaRNN	Benign	0.31	T;T
MetaSVM	Uncertain	-0.15	T
MutationAssessor	Benign	0.63	N;.
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-1.1	N;N
REVEL	Benign	0.29
Sift	Benign	0.18	T;T
Sift4G	Benign	0.27	T;T
Polyphen		0.0010	B;.
Vest4		0.20
MutPred		0.64		Loss of MoRF binding (P = 0.0616);.;
MVP		0.81
MPC		0.74
ClinPred		0.65	D
GERP RS		5.9
Varity_R		0.34
gMVP		0.86

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: rs17683430; hg19: chr22-32487700;