chr16-24891024-G-T

Position:

• chr16-24891024-G-T

Variant summary

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

The NM_001352248.3(SLC5A11):​c.820G>T​(p.Val274Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,886 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: SLC5A11 NM_001352248.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.84

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/exons	MANE	UniProt
SLC5A11	NM_001352248.3	c.820G>T	p.Val274Phe	missense_variant	10/17	ENST00000424767.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC5A11	ENST00000424767.7	c.820G>T	p.Val274Phe	missense_variant	10/17	2	NM_001352248.3	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1461886 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 727244

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000629

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 09, 2024

The c.820G>T (p.V274F) alteration is located in exon 9 (coding exon 8) of the SLC5A11 gene. This alteration results from a G to T substitution at nucleotide position 820, causing the valine (V) at amino acid position 274 to be replaced by a phenylalanine (F). 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	Benign	0.24
BayesDel_addAF	Uncertain	0.049	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.043	T;.;.;.;.;.
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.33
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.58	T;T;T;T;.;.
M_CAP	Uncertain	0.12	D
MetaRNN	Uncertain	0.48	T;T;T;T;T;T
MetaSVM	Uncertain	-0.26	T
MutationAssessor	Benign	1.6	L;.;.;.;.;.
MutationTaster	Benign	1.0	D;D;D;D;D;D;D;D;D
PrimateAI	Benign	0.42	T
PROVEAN	Uncertain	-2.6	D;D;D;D;D;D
REVEL	Uncertain	0.51
Sift	Benign	0.68	T;T;T;T;T;T
Sift4G	Benign	0.54	T;T;T;T;T;T
Polyphen		0.72	P;.;B;.;.;B
Vest4		0.60
MutPred		0.28		Loss of sheet (P = 0.0817);.;.;.;.;.;
MVP		0.53
MPC		0.60
ClinPred		0.90	D
GERP RS		2.1
Varity_R		0.26
gMVP		0.88

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: rs769393472; hg19: chr16-24902345;