16-24858708-A-T

Variant names:

• chr16-24858708-A-T
• rs1458812897
• NM_001352248.3:c.65A>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001352235.2(SLC5A11):​c.-67A>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,630 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SLC5A11 NM_001352235.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.600
• Publications: 0 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25074804).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001352235.2. 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.65A>T	p.Lys22Met	missense	Exon 3 of 17	NP_001339177.1	Q8WWX8-1
	SLC5A11	NM_001352235.2		c.-67A>T		5_prime_UTR_premature_start_codon_gain	Exon 3 of 18	NP_001339164.1
	SLC5A11	NM_001352249.2		c.-329A>T		5_prime_UTR_premature_start_codon_gain	Exon 3 of 19	NP_001339178.1	Q8WWX8-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC5A11	ENST00000424767.7	TSL:2 MANE Select	c.65A>T	p.Lys22Met	missense	Exon 3 of 17	ENSP00000416782.3	Q8WWX8-1
	SLC5A11	ENST00000347898.7	TSL:1	c.65A>T	p.Lys22Met	missense	Exon 2 of 16	ENSP00000289932.3	Q8WWX8-1
	SLC5A11	ENST00000565769.5	TSL:1	c.-57-3893A>T		intron	N/A	ENSP00000457179.1	Q8WWX8-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000399 AC: 1 AN: 250356 AF XY: 0.00000739

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459630 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726042

African (AFR) AF: 0.00 AC: 0 AN: 33436

American (AMR) AF: 0.00 AC: 0 AN: 44616

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 85872

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53408

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4566

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111652

Other (OTH) AF: 0.00 AC: 0 AN: 60256

GnomAD4 genome Cov.: 32

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	0.17
BayesDel_addAF	Benign	-0.015	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.022	T
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.35
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.85	T
M_CAP	Uncertain	0.091	D
MetaRNN	Benign	0.25	T
MetaSVM	Uncertain	-0.27	T
MutationAssessor	Benign	1.5	L
PhyloP100		0.60
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.28
Sift	Benign	0.081	T
Sift4G	Benign	0.092	T
Polyphen		0.73	P
Vest4		0.38
MutPred		0.44		Loss of solvent accessibility (P = 0.002)
MVP		0.76
MPC		0.47
ClinPred		0.65	D
GERP RS		0.58
Varity_R		0.10
gMVP		0.43

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: rs1458812897; hg19: chr16-24870029;