rs147458082

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_StrongBS1BS2

The NM_001003841.3(SLC6A19):c.41G>A(p.Arg14Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00126 in 1,610,690 control chromosomes in the GnomAD database, including 32 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R14W) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0018 ( 7 hom., cov: 34)

Exomes 𝑓: 0.0012 ( 25 hom. )

Consequence

SLC6A19
NM_001003841.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 6.42

Publications

7 publications found

Variant links:

Genes affected

SLC6A19 (HGNC:27960): (solute carrier family 6 member 19) This gene encodes a system B(0) transmembrane protein that actively transports most neutral amino acids across the apical membrane of epithelial cells. Mutations in this gene may result in Hartnup disorder, an inherited disease with symptoms such as pellagra, cerebellar ataxia, and psychosis. The expression and function of B0AT1 (SLC6A19) in intestinal cells depends on the presence of the accessory protein angiotensin-converting enzyme 2 (ACE2) which, among other functions, acts as a chaperone for membrane trafficking of B0AT1. The ACE2 is also the cellular receptor for severe acute respiratory syndrome-coronavirus (SARS-CoV) and for SARS-CoV-2 that is causing the coronavirus 2019 (COVID-19) pandemic [provided by RefSeq, Jul 2020]

SLC6A19 Gene-Disease associations (from GenCC):

Hartnup disease
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Labcorp Genetics (formerly Invitae), ClinGen

SLC6A19 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=0.0055764914).

BP6

Variant 5-1201691-G-A is Benign according to our data. Variant chr5-1201691-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 445301.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00181 (275/152314) while in subpopulation EAS AF = 0.039 (202/5180). AF 95% confidence interval is 0.0346. There are 7 homozygotes in GnomAd4. There are 160 alleles in the male GnomAd4 subpopulation. Median coverage is 34. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC6A19	NM_001003841.3 link	c.41G>A	p.Arg14Gln	missense_variant	Exon 1 of 12	ENST00000304460.11	NP_001003841.1	Q695T7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC6A19	ENST00000304460.11 link	c.41G>A	p.Arg14Gln	missense_variant	Exon 1 of 12	1	NM_001003841.3	ENSP00000305302.10		Q695T7
SLC6A19	ENST00000515652.5 link	n.41G>A		non_coding_transcript_exon_variant	Exon 1 of 11	2		ENSP00000425701.1		E9PD72

Frequencies

GnomAD3 genomes

AF:

0.00182

AC:

277

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000845

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0387

Gnomad SAS

AF:

0.00704

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00239

GnomAD2 exomes

AF:

0.00358

AC:

880

AN:

245624

AF XY:

0.00334

show subpopulations

Gnomad AFR exome

AF:

0.00101

Gnomad AMR exome

AF:

0.000203

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0374

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000629

Gnomad OTH exome

AF:

0.00233

GnomAD4 exome

AF:

0.00121

AC:

1761

AN:

1458376

Hom.:

Cov.:

AF XY:

0.00130

AC XY:

942

AN XY:

725654

show subpopulations

African (AFR)

AF:

0.000299

AC:

AN:

33460

American (AMR)

AF:

0.000157

AC:

AN:

44684

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26102

East Asian (EAS)

AF:

0.0281

AC:

1113

AN:

39666

South Asian (SAS)

AF:

0.00476

AC:

410

AN:

86196

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50524

Middle Eastern (MID)

AF:

0.00248

AC:

AN:

5654

European-Non Finnish (NFE)

AF:

0.0000819

AC:

AN:

1111780

Other (OTH)

AF:

0.00192

AC:

116

AN:

60310

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

128

255

383

510

638

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

128

160

<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:

0.00181

AC:

275

AN:

152314

Hom.:

Cov.:

AF XY:

0.00215

AC XY:

160

AN XY:

74476

show subpopulations

African (AFR)

AF:

0.000842

AC:

AN:

41564

American (AMR)

AF:

0.0000653

AC:

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.0390

AC:

202

AN:

5180

South Asian (SAS)

AF:

0.00684

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68018

Other (OTH)

AF:

0.00142

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

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:

0.00130

Hom.:

Bravo

AF:

0.00208

ESP6500AA

AF:

0.000911

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00371

AC:

449

Asia WGS

AF:

0.0280

AC:

AN:

3478

EpiCase

AF:

0.000273

EpiControl

AF:

0.00

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Aug 08, 2017

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 21, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.11

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.11

Eigen

Uncertain

0.31

Eigen_PC

Uncertain

0.28

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.96

MetaRNN

Benign

0.0056

MetaSVM

Benign

-0.62

MutationAssessor

Uncertain

2.4

PhyloP100

6.4

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-0.51

REVEL

Uncertain

0.36

Sift

Benign

0.38

Sift4G

Benign

0.43

Polyphen

1.0

Vest4

0.42

MVP

0.84

MPC

0.80

ClinPred

0.031

GERP RS

4.0

PromoterAI

-0.018

Neutral

(source)

Varity_R

0.22

gMVP

0.65

Mutation Taster

=71/29

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over