rs1395

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

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

Publications

86 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=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 VariationId 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.

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.1442C>T	p.Ser481Phe	missense	Exon 14 of 17	NP_066918.2	Q9Y289
	SLC5A6	NR_028323.2		n.2250C>T		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.1442C>T	p.Ser481Phe	missense	Exon 14 of 17	ENSP00000310208.3	Q9Y289
SLC5A6	ENST00000408041.5	TSL:1	c.1442C>T	p.Ser481Phe	missense	Exon 15 of 18	ENSP00000384853.1	Q9Y289
SLC5A6	ENST00000892752.1		c.1475C>T	p.Ser492Phe	missense	Exon 14 of 17	ENSP00000562811.1

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

GnomAD2 exomes

AF:

0.621

AC:

155858

AN:

251036

AF XY:

0.632

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 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

African (AFR)

AF:

0.219

AC:

7348

AN:

33478

American (AMR)

AF:

0.437

AC:

19530

AN:

44684

Ashkenazi Jewish (ASJ)

AF:

0.646

AC:

16881

AN:

26134

East Asian (EAS)

AF:

0.877

AC:

34785

AN:

39684

South Asian (SAS)

AF:

0.567

AC:

48909

AN:

86254

European-Finnish (FIN)

AF:

0.704

AC:

37606

AN:

53414

Middle Eastern (MID)

AF:

0.581

AC:

3350

AN:

5768

European-Non Finnish (NFE)

AF:

0.698

AC:

775714

AN:

1111800

Other (OTH)

AF:

0.646

AC:

39018

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

17252

34504

51757

69009

86261

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19396

38792

58188

77584

96980

<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:

0.555

AC:

84388

AN:

152066

Hom.:

26764

Cov.:

AF XY:

0.559

AC XY:

41527

AN XY:

74346

show subpopulations

African (AFR)

AF:

0.242

AC:

10034

AN:

41472

American (AMR)

AF:

0.520

AC:

7945

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.644

AC:

2235

AN:

3472

East Asian (EAS)

AF:

0.857

AC:

4419

AN:

5156

South Asian (SAS)

AF:

0.568

AC:

2739

AN:

4822

European-Finnish (FIN)

AF:

0.714

AC:

7563

AN:

10594

Middle Eastern (MID)

AF:

0.575

AC:

169

AN:

294

European-Non Finnish (NFE)

AF:

0.698

AC:

47449

AN:

67950

Other (OTH)

AF:

0.574

AC:

1214

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1621

3242

4862

6483

8104

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

694

1388

2082

2776

3470

<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:

0.653

Hom.:

161068

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

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

0.089

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.31

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.019

Eigen

Benign

-0.24

Eigen_PC

Benign

-0.15

FATHMM_MKL

Benign

0.70

LIST_S2

Benign

0.47

MetaRNN

Benign

9.6e-7

MetaSVM

Benign

-0.92

MutationAssessor

Uncertain

2.8

PhyloP100

1.0

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.96

REVEL

Benign

0.20

Sift

Benign

0.040

Sift4G

Uncertain

0.053

Polyphen

0.012

Vest4

0.084

MPC

0.38

ClinPred

0.035

GERP RS

4.8

Varity_R

0.066

gMVP

0.37

Mutation Taster

=100/0

polymorphism (auto)

(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