22-32043334-A-G

Variant names:

• chr22-32043334-A-G
• NM_000343.4:c.53A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000343.4(SLC5A1):​c.53A>G​(p.Glu18Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. E18E) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC5A1 NM_000343.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.77
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11142528).

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.53A>G	p.Glu18Gly	missense	Exon 1 of 15	NP_000334.1	P13866-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC5A1	ENST00000266088.9	TSL:1 MANE Select	c.53A>G	p.Glu18Gly	missense	Exon 1 of 15	ENSP00000266088.4	P13866-1
	SLC5A1	ENST00000878506.1		c.53A>G	p.Glu18Gly	missense	Exon 1 of 14	ENSP00000548565.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	0.44
DANN	Benign	0.75
DEOGEN2	Benign	0.072	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.053	N
LIST_S2	Benign	0.31	T
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.72	T
MutationAssessor	Benign	1.1	L
PhyloP100		-1.8
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.92	N
REVEL	Benign	0.14
Sift	Benign	0.26	T
Sift4G	Benign	0.24	T
Polyphen		0.010	B
Vest4		0.13
MutPred		0.30		Loss of disorder (P = 0.0873)
MVP		0.47
MPC		0.57
ClinPred		0.22	T
GERP RS		-6.3
PromoterAI		-0.044	Neutral
Varity_R		0.037
gMVP		0.29
Mutation Taster		=96/4	polymorphism

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

hg19: chr22-32439321;