16-24898098-T-G

Variant names:

• chr16-24898098-T-G
• rs1430141548
• NM_001352248.3:c.995T>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001352248.3(SLC5A11):​c.995T>G​(p.Ile332Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC5A11 NM_001352248.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.01

Genes affected

SLC5A11 (HGNC:23091): (solute carrier family 5 member 11) Cotransporters, such as SLC5A11, represent a major class of proteins that make use of ion gradients to drive active transport for the cellular accumulation of nutrients, neurotransmitters, osmolytes, and ions Roll et al. (2002) [PubMed 12039040].[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC5A11	NM_001352248.3	c.995T>G	p.Ile332Ser	missense_variant	Exon 11 of 17	ENST00000424767.7	NP_001339177.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC5A11	ENST00000424767.7	c.995T>G	p.Ile332Ser	missense_variant	Exon 11 of 17	2	NM_001352248.3	ENSP00000416782.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 09, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.995T>G (p.I332S) alteration is located in exon 10 (coding exon 9) of the SLC5A11 gene. This alteration results from a T to G substitution at nucleotide position 995, causing the isoleucine (I) at amino acid position 332 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.39
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Uncertain	0.020
CADD	Benign	20
DANN	Uncertain	0.99
Eigen	Benign	0.00016
Eigen_PC	Benign	0.14
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.18	T;.
M_CAP	Benign	0.069	D
MetaRNN	Uncertain	0.47	T;T
MetaSVM	Uncertain	0.057	D
PROVEAN	Benign	0.92	N;N
REVEL	Uncertain	0.35
Sift	Benign	0.29	T;T
Sift4G	Benign	0.60	T;T
Vest4		0.38
MutPred		0.74		Gain of glycosylation at P202 (P = 0.0894);Gain of glycosylation at P202 (P = 0.0894);
MVP		0.76
ClinPred		0.85	D
GERP RS		5.5

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

Publications

LitVar

Other links and lift over

dbSNP: rs1430141548; hg19: chr16-24909419;