SLC5A1 p.His615Gln

Variant names:

• chr22-32110063-C-A
• NM_000343.4:c.1845C>A
• SLC5A1 p.His615Gln

Your query was ambiguous. Multiple possible variants found:

• chr22-32110063-C-A
• chr22-32110063-C-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000343.4(SLC5A1):​c.1845C>A​(p.His615Gln) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Benign in ClinVar. Synonymous variant affecting the same amino acid position (i.e. H615H) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC5A1 NM_000343.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.134
• 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, Orphanet, Labcorp Genetics (formerly Invitae), PanelApp Australia

LOC105373000 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.039004385).

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.1845C>A	p.His615Gln	missense	Exon 15 of 15	NP_000334.1	P13866-1
	SLC5A1	NM_001256314.2		c.1464C>A	p.His488Gln	missense	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.1845C>A	p.His615Gln	missense	Exon 15 of 15	ENSP00000266088.4	P13866-1
	SLC5A1	ENST00000878506.1		c.1737C>A	p.His579Gln	missense	Exon 14 of 14	ENSP00000548565.1
	SLC5A1	ENST00000543737.2	TSL:2	c.1464C>A	p.His488Gln	missense	Exon 14 of 14	ENSP00000444898.1	P13866-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	6.6
DANN	Benign	0.24
DEOGEN2	Benign	0.041	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.95
FATHMM_MKL	Benign	0.47	N
LIST_S2	Benign	0.010	T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.039	T
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	-2.0	N
PhyloP100		0.13
PrimateAI	Benign	0.31	T
PROVEAN	Benign	1.4	N
REVEL	Benign	0.20
Sift	Benign	0.65	T
Sift4G	Benign	0.79	T
Varity_R		0.040
gMVP		0.14
Mutation Taster		=98/2	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

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

Other links and lift over

hg19: chr22-32506050;