16-24875669-A-T

Position:

• chr16-24875669-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001352248.3(SLC5A11):​c.415A>T​(p.Ile139Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SLC5A11 NM_001352248.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.49

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13785994).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC5A11	NM_001352248.3	c.415A>T	p.Ile139Phe	missense_variant	7/17	ENST00000424767.7	NP_001339177.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC5A11	ENST00000424767.7	c.415A>T	p.Ile139Phe	missense_variant	7/17	2	NM_001352248.3	ENSP00000416782	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1461802 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727192

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

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

Nov 29, 2023

The c.415A>T (p.I139F) alteration is located in exon 6 (coding exon 5) of the SLC5A11 gene. This alteration results from a A to T substitution at nucleotide position 415, causing the isoleucine (I) at amino acid position 139 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	0.087
BayesDel_addAF	Benign	-0.077	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	17
DANN	Benign	0.43
DEOGEN2	Benign	0.0094	T;.;.;.
Eigen	Benign	-0.81
Eigen_PC	Benign	-0.85
FATHMM_MKL	Benign	0.55	D
LIST_S2	Benign	0.45	T;T;T;.
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.14	T;T;T;T
MetaSVM	Benign	-0.34	T
MutationAssessor	Benign	-0.11	N;.;.;.
MutationTaster	Benign	1.0	N;N;N;N;N;N;N;N;N
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.040	N;N;N;N
REVEL	Benign	0.27
Sift	Uncertain	0.0050	D;D;D;D
Sift4G	Benign	0.12	T;D;T;D
Polyphen		0.071	B;.;.;.
Vest4		0.22
MutPred		0.26		Gain of methylation at R140 (P = 0.0447);.;.;.;
MVP		0.53
MPC		0.35
ClinPred		0.37	T
GERP RS		2.2
Varity_R		0.090
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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-24886990;