Variant 2-27201735-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_021095.4(SLC5A6):c.1475G>A(p.Ser492Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00129 in 1,614,160 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 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 0.0066 ( 10 hom., cov: 32)

Exomes 𝑓: 0.00074 ( 13 hom. )

Consequence

SLC5A6
NM_021095.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.931

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=0.002195239).

BP6

Variant 2-27201735-C-T is Benign according to our data. Variant chr2-27201735-C-T is described in ClinVar as [Benign]. Clinvar id is 788951.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00664 (1012/152306) while in subpopulation AFR AF= 0.0231 (960/41564). AF 95% confidence interval is 0.0219. There are 10 homozygotes in gnomad4. There are 511 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC5A6	NM_021095.4 linkuse as main transcript	c.1475G>A	p.Ser492Asn	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.1475G>A	p.Ser492Asn	missense_variant	14/17	1	NM_021095.4	ENSP00000310208.3		Q9Y289

Frequencies

GnomAD3 genomes

AF:

0.00662

AC:

1007

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0230

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00223

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00479

GnomAD3 exomes

AF:

0.00164

AC:

411

AN:

251368

Hom.:

AF XY:

0.00120

AC XY:

163

AN XY:

135850

show subpopulations

Gnomad AFR exome

AF:

0.0238

Gnomad AMR exome

AF:

0.000521

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.000736

AC:

1076

AN:

1461854

Hom.:

Cov.:

AF XY:

0.000605

AC XY:

440

AN XY:

727222

show subpopulations

Gnomad4 AFR exome

AF:

0.0279

Gnomad4 AMR exome

AF:

0.000559

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000104

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000719

Gnomad4 OTH exome

AF:

0.00132

GnomAD4 genome

AF:

0.00664

AC:

1012

AN:

152306

Hom.:

Cov.:

AF XY:

0.00686

AC XY:

511

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.0231

Gnomad4 AMR

AF:

0.00222

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00474

Alfa

AF:

0.00153

Hom.:

Bravo

AF:

0.00745

ESP6500AA

AF:

0.0209

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00207

AC:

251

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

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	Labcorp Genetics (formerly Invitae), Labcorp	Dec 26, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.57

CADD

Benign

3.0

DANN

Benign

0.23

DEOGEN2

Benign

0.0057

T;T

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.077

LIST_S2

Benign

0.36

.;T

MetaRNN

Benign

0.0022

T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.95

L;L

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.49

N;N

REVEL

Benign

0.14

Sift

Benign

0.54

T;T

Sift4G

Benign

0.63

T;T

Polyphen

0.0

B;B

Vest4

0.077

MVP

0.14

MPC

0.33

ClinPred

0.00064

GERP RS

-1.8

Varity_R

0.020

gMVP

0.19

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