chr16-31490116-G-T

Position:

• chr16-31490116-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_003041.4(SLC5A2):​c.1678G>T​(p.Val560Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SLC5A2 NM_003041.4 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 9.27

Genes affected

SLC5A2 (HGNC:11037): (solute carrier family 5 member 2) This gene encodes a member of the sodium glucose cotransporter family which are sodium-dependent glucose transport proteins. The encoded protein is the major cotransporter involved in glucose reabsorption in the kidney. Mutations in this gene are associated with renal glucosuria. Two transcript variants, one protein-coding and one not, have been found for this gene. [provided by RefSeq, Feb 2015]

RUSF1 (HGNC:25848): (RUS family member 1) This gene encodes a putative transmembrane protein containing a conserved DUF647 domain that may be involved in protein-protein interaction. The encoded protein is related to a plant protein that participates in ultraviolet B light-sensing during root morphogenesis. [provided by RefSeq, Feb 2013]

SLC5A2 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.814

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC5A2	NM_003041.4	c.1678G>T	p.Val560Phe	missense_variant	13/14	ENST00000330498.4	NP_003032.1
RUSF1	NM_022744.4	c.*719C>A		3_prime_UTR_variant	13/13	ENST00000327237.7	NP_073581.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC5A2	ENST00000330498.4	c.1678G>T	p.Val560Phe	missense_variant	13/14	1	NM_003041.4	ENSP00000327943.3
RUSF1	ENST00000327237	c.*719C>A		3_prime_UTR_variant	13/13	1	NM_022744.4	ENSP00000317579.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

SLC5A2-related disorder Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 05, 2024

The SLC5A2 c.1678G>T variant is predicted to result in the amino acid substitution p.Val560Phe. To our knowledge, this variant has not been reported in the literature or in a large population database, indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.87
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.10
CADD	Pathogenic	33
DANN	Uncertain	0.99
DEOGEN2	Benign	0.38	T
Eigen	Uncertain	0.21
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Uncertain	0.92	D
M_CAP	Uncertain	0.22	D
MetaRNN	Pathogenic	0.81	D
MetaSVM	Benign	-0.40	T
MutationAssessor	Uncertain	2.4	M
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-2.1	N
REVEL	Uncertain	0.60
Sift	Uncertain	0.0090	D
Sift4G	Benign	0.10	T
Polyphen		0.45	P
Vest4		0.87
MutPred		0.47		Loss of helix (P = 0.0376);
MVP		0.93
MPC		0.69
ClinPred		0.97	D
GERP RS		4.3
Varity_R		0.22
gMVP		0.90

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.35		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.35		Position offset: 8

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-31501437;