2-27201768-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_021095.4(SLC5A6):c.1442C>T(p.Ser481Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.662 in 1,613,668 control chromosomes in the GnomAD database, including 364,575 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.55 (26764 hom., cov: 32)
  • Exomes 𝑓: 0.67 (337811 hom.)
• Consequence: SLC5A6 NM_021095.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.00

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 Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=9.574699E-7).
• BP6: Variant 2-27201768-G-A is Benign according to our data. Variant chr2-27201768-G-A is described in ClinVar as [Benign]. Clinvar id is 1256723.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.836 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC5A6	NM_021095.4	c.1442C>T	p.Ser481Phe	missense_variant	14/17	ENST00000310574.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC5A6	ENST00000310574.8	c.1442C>T	p.Ser481Phe	missense_variant	14/17	1	NM_021095.4	P1

Frequencies

GnomAD3 genomes AF: 0.555 AC: 84401 AN: 151948 Hom.: 26779 Cov.: 32

Gnomad AFR AF: 0.242

Gnomad AMI AF: 0.682

Gnomad AMR AF: 0.520

Gnomad ASJ AF: 0.644

Gnomad EAS AF: 0.858

Gnomad SAS AF: 0.569

Gnomad FIN AF: 0.714

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.698

Gnomad OTH AF: 0.577

GnomAD3 exomes AF: 0.621 AC: 155858 AN: 251036 Hom.: 51179 AF XY: 0.632 AC XY: 85771 AN XY: 135710

Gnomad AFR exome AF: 0.229

Gnomad AMR exome AF: 0.430

Gnomad ASJ exome AF: 0.647

Gnomad EAS exome AF: 0.853

Gnomad SAS exome AF: 0.563

Gnomad FIN exome AF: 0.709

Gnomad NFE exome AF: 0.693

Gnomad OTH exome AF: 0.628

GnomAD4 exome AF: 0.673 AC: 983141 AN: 1461602 Hom.: 337811 Cov.: 52 AF XY: 0.672 AC XY: 488289 AN XY: 727114

Gnomad4 AFR exome AF: 0.219

Gnomad4 AMR exome AF: 0.437

Gnomad4 ASJ exome AF: 0.646

Gnomad4 EAS exome AF: 0.877

Gnomad4 SAS exome AF: 0.567

Gnomad4 FIN exome AF: 0.704

Gnomad4 NFE exome AF: 0.698

Gnomad4 OTH exome AF: 0.646

GnomAD4 genome AF: 0.555 AC: 84388 AN: 152066 Hom.: 26764 Cov.: 32 AF XY: 0.559 AC XY: 41527 AN XY: 74346

Gnomad4 AFR AF: 0.242

Gnomad4 AMR AF: 0.520

Gnomad4 ASJ AF: 0.644

Gnomad4 EAS AF: 0.857

Gnomad4 SAS AF: 0.568

Gnomad4 FIN AF: 0.714

Gnomad4 NFE AF: 0.698

Gnomad4 OTH AF: 0.574

Alfa AF: 0.672 Hom.: 89762

Bravo AF: 0.526

TwinsUK AF: 0.715 AC: 2653

ALSPAC AF: 0.704 AC: 2712

ESP6500AA AF: 0.251 AC: 1108

ESP6500EA AF: 0.690 AC: 5933

ExAC AF: 0.618 AC: 75056

Asia WGS AF: 0.645 AC: 2246 AN: 3478

EpiCase AF: 0.705

EpiControl AF: 0.694

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 02, 2020

This variant is associated with the following publications: (PMID: 28008009) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.31
Cadd	Benign	17
Dann	Uncertain	0.99
DEOGEN2	Benign	0.019	T;T
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.15
FATHMM_MKL	Benign	0.70	D
MetaRNN	Benign	9.6e-7	T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Uncertain	2.8	M;M
MutationTaster	Benign	0.072	P;P
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.96	N;N
REVEL	Benign	0.20
Sift	Benign	0.040	D;D
Sift4G	Uncertain	0.053	T;T
Polyphen		0.012	B;B
Vest4		0.084
MPC		0.38
ClinPred		0.035	T
GERP RS		4.8
Varity_R		0.066
gMVP		0.37

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

LitVar

Other links and lift over

dbSNP: rs1395; hg19: chr2-27424636; COSMIC: COSV60160327; COSMIC: COSV60160327;