2-27201669-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_021095.4(SLC5A6):c.1541C>T(p.Ser514Phe) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC5A6 NM_021095.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.81

Genes affected

SLC5A6 (HGNC:11041): (solute carrier family 5 member 6) Enables biotin transmembrane transporter activity and pantothenate transmembrane transporter activity. Involved in anion transmembrane transport and transport across blood-brain barrier. Located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2880922).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC5A6	NM_021095.4	c.1541C>T	p.Ser514Phe	missense_variant	14/17	ENST00000310574.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC5A6	ENST00000310574.8	c.1541C>T	p.Ser514Phe	missense_variant	14/17	1	NM_021095.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 10, 2023

The c.1541C>T (p.S514F) alteration is located in exon 14 (coding exon 12) of the SLC5A6 gene. This alteration results from a C to T substitution at nucleotide position 1541, causing the serine (S) at amino acid position 514 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	0.11
BayesDel_addAF	Benign	-0.044	T
BayesDel_noAF	Benign	-0.30
Cadd	Benign	22
Dann	Uncertain	0.99
DEOGEN2	Benign	0.031	T;T
Eigen	Uncertain	0.31
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Uncertain	0.93	D
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.29	T;T
MetaSVM	Benign	-0.55	T
MutationAssessor	Uncertain	2.6	M;M
MutationTaster	Benign	1.0	D;D
PrimateAI	Benign	0.39	T
PROVEAN	Uncertain	-2.5	D;D
REVEL	Benign	0.21
Sift	Benign	0.036	D;D
Sift4G	Uncertain	0.020	D;D
Polyphen		0.59	P;P
Vest4		0.33
MutPred		0.44		Loss of disorder (P = 0.0319);Loss of disorder (P = 0.0319);
MVP		0.48
MPC		0.55
ClinPred		0.84	D
GERP RS		5.9
Varity_R		0.13
gMVP		0.27

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: chr2-27424537;