chr16-24891024-G-T

Variant names:

• chr16-24891024-G-T
• rs769393472
• NM_001352248.3:c.820G>T

Variant summary

Our verdict is Uncertain significance. The variant received 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V274I) has been classified as Likely benign.

• 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
• Publications: 1 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001352248.3. 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
	SLC5A11	NM_001352248.3	MANE Select	c.820G>T	p.Val274Phe	missense	Exon 10 of 17	NP_001339177.1	Q8WWX8-1
	SLC5A11	NM_001352242.2		c.820G>T	p.Val274Phe	missense	Exon 10 of 17	NP_001339171.1	Q8WWX8-1
	SLC5A11	NM_001352235.2		c.781G>T	p.Val261Phe	missense	Exon 11 of 18	NP_001339164.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC5A11	ENST00000424767.7	TSL:2 MANE Select	c.820G>T	p.Val274Phe	missense	Exon 10 of 17	ENSP00000416782.3	Q8WWX8-1
	SLC5A11	ENST00000347898.7	TSL:1	c.820G>T	p.Val274Phe	missense	Exon 9 of 16	ENSP00000289932.3	Q8WWX8-1
	SLC5A11	ENST00000565769.5	TSL:1	c.628G>T	p.Val210Phe	missense	Exon 9 of 16	ENSP00000457179.1	Q8WWX8-3

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

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000629 AC: 7 AN: 1112010

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 31

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Uncertain	0.12	D
MetaRNN	Uncertain	0.48	T
MetaSVM	Uncertain	-0.26	T
MutationAssessor	Benign	1.6	L
PhyloP100		1.8
PrimateAI	Benign	0.42	T
PROVEAN	Uncertain	-2.6	D
REVEL	Uncertain	0.51
Sift	Benign	0.68	T
Sift4G	Benign	0.54	T
Polyphen		0.72	P
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
Mutation Taster		=62/38	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

dbSNP: rs769393472; hg19: chr16-24902345;