Variant 5-1201643-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_StrongBA1

The NM_001003841.3(SLC6A19):c.-8C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0107 in 1,603,324 control chromosomes in the GnomAD database, including 1,589 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.057 ( 827 hom., cov: 34)

Exomes 𝑓: 0.0059 ( 762 hom. )

Consequence

SLC6A19
NM_001003841.3 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.719

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 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 (BayesDel_noAF=-0.84).

BP6

Variant 5-1201643-C-T is Benign according to our data. Variant chr5-1201643-C-T is described in ClinVar as [Benign]. Clinvar id is 1279037.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-1201643-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.195 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC6A19	NM_001003841.3 link	c.-8C>T		5_prime_UTR_variant	Exon 1 of 12	ENST00000304460.11	NP_001003841.1	Q695T7

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
SLC6A19	ENST00000304460 link	c.-8C>T	5_prime_UTR_variant	Exon 1 of 12	1	NM_001003841.3	ENSP00000305302.10	Q695T7
SLC6A19	ENST00000515652.5 link	n.-8C>T	non_coding_transcript_exon_variant	Exon 1 of 11	2		ENSP00000425701.1	E9PD72
SLC6A19	ENST00000515652.5 link	n.-8C>T	5_prime_UTR_variant	Exon 1 of 11	2		ENSP00000425701.1	E9PD72

Frequencies

GnomAD3 genomes

AF:

0.0570

AC:

8675

AN:

152150

Hom.:

825

Cov.:

show subpopulations

Gnomad AFR

AF:

0.199

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0192

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00165

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.000750

Gnomad OTH

AF:

0.0411

GnomAD3 exomes

AF:

0.0144

AC:

3396

AN:

235798

Hom.:

327

AF XY:

0.0105

AC XY:

1356

AN XY:

129140

show subpopulations

Gnomad AFR exome

AF:

0.201

Gnomad AMR exome

AF:

0.00824

Gnomad ASJ exome

AF:

0.000102

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000501

Gnomad FIN exome

AF:

0.0000647

Gnomad NFE exome

AF:

0.000538

Gnomad OTH exome

AF:

0.00754

GnomAD4 exome

AF:

0.00586

AC:

8507

AN:

1451056

Hom.:

762

Cov.:

AF XY:

0.00507

AC XY:

3659

AN XY:

721960

show subpopulations

Gnomad4 AFR exome

AF:

0.203

Gnomad4 AMR exome

AF:

0.00962

Gnomad4 ASJ exome

AF:

0.0000384

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.000677

Gnomad4 FIN exome

AF:

0.0000864

Gnomad4 NFE exome

AF:

0.000368

Gnomad4 OTH exome

AF:

0.0131

GnomAD4 genome

AF:

0.0571

AC:

8695

AN:

152268

Hom.:

827

Cov.:

AF XY:

0.0543

AC XY:

4043

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.199

Gnomad4 AMR

AF:

0.0192

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000750

Gnomad4 OTH

AF:

0.0406

Alfa

AF:

0.0282

Hom.:

131

Bravo

AF:

0.0650

Asia WGS

AF:

0.0100

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

May 23, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

SLC6A19-related disorder

Benign:1

Jan 20, 2020

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

4.5

DANN

Benign

0.70

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