2-27201735-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -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. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

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

Publications

7 publications found

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 Gene-Disease associations (from GenCC):

neurodegeneration, infantile-onset, biotin-responsive
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics, PanelApp Australia
peripheral motor neuropathy, childhood-onset, biotin-responsive
Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia
inherited neurodegenerative disorder
Inheritance: AR Classification: MODERATE Submitted by: Illumina

SLC5A6 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 10 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021095.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC5A6	NM_021095.4	MANE Select	c.1475G>A	p.Ser492Asn	missense	Exon 14 of 17	NP_066918.2	Q9Y289
	SLC5A6	NR_028323.2		n.2283G>A		non_coding_transcript_exon	Exon 13 of 17

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC5A6	ENST00000310574.8	TSL:1 MANE Select	c.1475G>A	p.Ser492Asn	missense	Exon 14 of 17	ENSP00000310208.3	Q9Y289
SLC5A6	ENST00000408041.5	TSL:1	c.1475G>A	p.Ser492Asn	missense	Exon 15 of 18	ENSP00000384853.1	Q9Y289
SLC5A6	ENST00000892752.1		c.1508G>A	p.Ser503Asn	missense	Exon 14 of 17	ENSP00000562811.1

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

GnomAD2 exomes

AF:

0.00164

AC:

411

AN:

251368

AF XY:

0.00120

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 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

African (AFR)

AF:

0.0279

AC:

934

AN:

33480

American (AMR)

AF:

0.000559

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.000104

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00347

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000719

AC:

AN:

1111980

Other (OTH)

AF:

0.00132

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

112

169

225

281

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

102

136

170

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00664

AC:

1012

AN:

152306

Hom.:

Cov.:

AF XY:

0.00686

AC XY:

511

AN XY:

74494

show subpopulations

African (AFR)

AF:

0.0231

AC:

960

AN:

41564

American (AMR)

AF:

0.00222

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.000415

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68024

Other (OTH)

AF:

0.00474

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

147

196

245

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00311

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

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.57

CADD

Benign

3.0

(source)

DANN

Benign

0.23

DEOGEN2

Benign

0.0057

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.077

LIST_S2

Benign

0.36

MetaRNN

Benign

0.0022

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.95

PhyloP100

-0.93

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.49

REVEL

Benign

0.14

Sift

Benign

0.54

Sift4G

Benign

0.63

Polyphen

0.0

Vest4

0.077

MVP

0.14

MPC

0.33

ClinPred

0.00064

GERP RS

-1.8

Varity_R

0.020

gMVP

0.19

Mutation Taster

=98/2

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over