Variant chr2-27201104-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.1658G>A(p.Arg553Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00219 in 1,611,090 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0021 ( 1 hom., cov: 31)

Exomes 𝑓: 0.0022 ( 7 hom. )

Consequence

SLC5A6
NM_021095.4 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.756

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:

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=0.0077798665).

BP6

Variant 2-27201104-C-T is Benign according to our data. Variant chr2-27201104-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 713562.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00208 (317/152174) while in subpopulation AMR AF= 0.00353 (54/15290). AF 95% confidence interval is 0.00278. There are 1 homozygotes in gnomad4. There are 156 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC5A6	NM_021095.4 link	c.1658G>A	p.Arg553Gln	missense_variant	16/17	ENST00000310574.8	NP_066918.2	Q9Y289Q9HD19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC5A6	ENST00000310574.8 link	c.1658G>A	p.Arg553Gln	missense_variant	16/17	1	NM_021095.4	ENSP00000310208.3		Q9Y289

Frequencies

GnomAD3 genomes

AF:

0.00208

AC:

317

AN:

152056

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000338

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00354

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00547

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00275

Gnomad OTH

AF:

0.000480

GnomAD3 exomes

AF:

0.00219

AC:

548

AN:

250030

Hom.:

AF XY:

0.00210

AC XY:

284

AN XY:

135056

show subpopulations

Gnomad AFR exome

AF:

0.0000616

Gnomad AMR exome

AF:

0.000727

Gnomad ASJ exome

AF:

0.00101

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000658

Gnomad FIN exome

AF:

0.00950

Gnomad NFE exome

AF:

0.00249

Gnomad OTH exome

AF:

0.00395

GnomAD4 exome

AF:

0.00220

AC:

3210

AN:

1458916

Hom.:

Cov.:

AF XY:

0.00222

AC XY:

1613

AN XY:

725796

show subpopulations

Gnomad4 AFR exome

AF:

0.000299

Gnomad4 AMR exome

AF:

0.000763

Gnomad4 ASJ exome

AF:

0.00138

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00967

Gnomad4 NFE exome

AF:

0.00223

Gnomad4 OTH exome

AF:

0.00209

GnomAD4 genome

AF:

0.00208

AC:

317

AN:

152174

Hom.:

Cov.:

AF XY:

0.00210

AC XY:

156

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.000337

Gnomad4 AMR

AF:

0.00353

Gnomad4 ASJ

AF:

0.000865

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00547

Gnomad4 NFE

AF:

0.00275

Gnomad4 OTH

AF:

0.000475

Alfa

AF:

0.00207

Hom.:

Bravo

AF:

0.00168

TwinsUK

AF:

0.00216

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00256

AC:

ExAC

AF:

0.00192

AC:

233

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00278

EpiControl

AF:

0.00249

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 01, 2018	- -

Neurodegeneration, infantile-onset, biotin-responsive

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Aug 12, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.011

T;T

Eigen

Benign

-0.39

Eigen_PC

Benign

-0.33

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.71

.;T

M_CAP

Benign

0.060

MetaRNN

Benign

0.0078

T;T

MetaSVM

Benign

-0.90

MutationAssessor

Uncertain

2.7

M;M

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.87

N;N

REVEL

Benign

0.069

Sift

Benign

0.061

T;T

Sift4G

Benign

0.10

T;T

Polyphen

0.40

B;B

Vest4

0.21

MVP

0.33

MPC

0.42

ClinPred

0.044

GERP RS

3.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.034

gMVP

0.28

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

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