5-1201643-C-T

Variant names:

• chr5-1201643-C-T
• rs67330201
• NM_001003841.3:c.-8C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.719

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]

ACMG classification

Our verdict: Benign. The variant received -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	c.-8C>T		5_prime_UTR_variant	Exon 1 of 12	ENST00000304460.11	NP_001003841.1

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.0570 AC: 8675 AN: 152150 Hom.: 825 Cov.: 34

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

GnomAD2 exomes AF: 0.0144 AC: 3396 AN: 235798 AF XY: 0.0105

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 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.: 31 AF XY: 0.00507 AC XY: 3659 AN XY: 721960

Gnomad4 AFR exome AF: 0.203 AC: 6774 AN: 33394

Gnomad4 AMR exome AF: 0.00962 AC: 427 AN: 44374

Gnomad4 ASJ exome AF: 0.0000384 AC: 1 AN: 26066

Gnomad4 EAS exome AF: 0.0000253 AC: 1 AN: 39596

Gnomad4 SAS exome AF: 0.000677 AC: 58 AN: 85668

Gnomad4 FIN exome AF: 0.0000864 AC: 4 AN: 46288

Gnomad4 NFE exome AF: 0.000368 AC: 409 AN: 1110810

Gnomad4 Remaining exome AF: 0.0131 AC: 786 AN: 60080

GnomAD4 genome AF: 0.0571 AC: 8695 AN: 152268 Hom.: 827 Cov.: 34 AF XY: 0.0543 AC XY: 4043 AN XY: 74452

Gnomad4 AFR AF: 0.199 AC: 0.19869 AN: 0.19869

Gnomad4 AMR AF: 0.0192 AC: 0.0192157 AN: 0.0192157

Gnomad4 ASJ AF: 0.000288 AC: 0.000288018 AN: 0.000288018

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.00145 AC: 0.00144928 AN: 0.00144928

Gnomad4 FIN AF: 0.00 AC: 0 AN: 0

Gnomad4 NFE AF: 0.000750 AC: 0.000749691 AN: 0.000749691

Gnomad4 OTH AF: 0.0406 AC: 0.0406427 AN: 0.0406427

Alfa AF: 0.0282 Hom.: 131

Bravo AF: 0.0650

Asia WGS AF: 0.0100 AC: 37 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

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
Mutation Taster		=298/2	polymorphism (auto)

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

Other links and lift over

dbSNP: rs67330201; hg19: chr5-1201758;