2-27201088-G-T

Position:

• chr2-27201088-G-T

Variant summary

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

The NM_021095.4(SLC5A6):​c.1674C>A​(p.Asn558Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 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)
• Consequence: SLC5A6 NM_021095.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.46

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=0.39001787).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC5A6	NM_021095.4	c.1674C>A	p.Asn558Lys	missense_variant	16/17	ENST00000310574.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC5A6	ENST00000310574.8	c.1674C>A	p.Asn558Lys	missense_variant	16/17	1	NM_021095.4	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

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

Aug 23, 2021

The c.1674C>A (p.N558K) alteration is located in exon 16 (coding exon 14) of the SLC5A6 gene. This alteration results from a C to A substitution at nucleotide position 1674, causing the asparagine (N) at amino acid position 558 to be replaced by a lysine (K). 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	0.22
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	17
DANN	Benign	0.93
DEOGEN2	Benign	0.034	T;T
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.32
FATHMM_MKL	Uncertain	0.92	D
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.39	T;T
MetaSVM	Uncertain	-0.27	T
MutationAssessor	Uncertain	2.7	M;M
MutationTaster	Benign	0.95	D;D
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-1.8	N;N
REVEL	Uncertain	0.34
Sift	Benign	0.15	T;T
Sift4G	Benign	0.24	T;T
Polyphen		0.034	B;B
Vest4		0.49
MutPred		0.53		Gain of methylation at N558 (P = 0.0259);Gain of methylation at N558 (P = 0.0259);
MVP		0.57
MPC		0.46
ClinPred		0.16	T
GERP RS		3.9
Varity_R		0.035
gMVP		0.46

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr2-27423956;