Variant 2-27201768-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.00

Variant links:

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]

SLC5A6 links:

SLC5A6 (HGNC:):

SLC5A6 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 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_multiple_submitters_no_conflicts, 2 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	Protein	UniProt
SLC5A6	NM_021095.4 linkuse as main transcript	c.1442C>T	p.Ser481Phe	missense_variant	14/17	ENST00000310574.8	NP_066918.2	Q9Y289Q9HD19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC5A6	ENST00000310574.8 linkuse as main transcript	c.1442C>T	p.Ser481Phe	missense_variant	14/17	1	NM_021095.4	ENSP00000310208.3		Q9Y289

Frequencies

GnomAD3 genomes

AF:

0.555

AC:

84401

AN:

151948

Hom.:

26779

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.672

AC XY:

488289

AN XY:

727114

show subpopulations

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.:

AF XY:

0.559

AC XY:

41527

AN XY:

74346

show subpopulations

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:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 02, 2020	This variant is associated with the following publications: (PMID: 28008009) -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.31

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.019

T;T

Eigen

Benign

-0.24

Eigen_PC

Benign

-0.15

FATHMM_MKL

Benign

0.70

LIST_S2

Benign

0.47

.;T

MetaRNN

Benign

9.6e-7

T;T

MetaSVM

Benign

-0.92

MutationAssessor

Uncertain

2.8

M;M

PrimateAI

Benign

0.33

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

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over