5-1201679-G-T

Variant names:

• chr5-1201679-G-T
• rs142954960
• NM_001003841.3:c.29G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001003841.3(SLC6A19):​c.29G>T​(p.Gly10Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000686 in 1,457,090 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G10S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SLC6A19 NM_001003841.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.41
• Publications: 1 publications found

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: Orphanet, ClinGen, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001003841.3. 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
	SLC6A19	NM_001003841.3	MANE Select	c.29G>T	p.Gly10Val	missense	Exon 1 of 12	NP_001003841.1	Q695T7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A19	ENST00000304460.11	TSL:1 MANE Select	c.29G>T	p.Gly10Val	missense	Exon 1 of 12	ENSP00000305302.10	Q695T7
	SLC6A19	ENST00000515652.5	TSL:2	n.29G>T		non_coding_transcript_exon	Exon 1 of 11	ENSP00000425701.1	E9PD72

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD2 exomes AF: 0.00000411 AC: 1 AN: 243186 AF XY: 0.00000753

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1457090 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 725034

African (AFR) AF: 0.00 AC: 0 AN: 33462

American (AMR) AF: 0.00 AC: 0 AN: 44660

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26100

East Asian (EAS) AF: 0.00 AC: 0 AN: 39668

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86136

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49548

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5554

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111700

Other (OTH) AF: 0.00 AC: 0 AN: 60262

GnomAD4 genome Cov.: 34

ExAC AF: 0.00000827 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Benign	-0.011	T
BayesDel_noAF	Benign	-0.15
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.22	T
Eigen	Uncertain	0.27
Eigen_PC	Benign	0.22
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.96	D
M_CAP	Uncertain	0.12	D
MetaRNN	Uncertain	0.65	D
MetaSVM	Uncertain	-0.28	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		4.4
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-1.9	N
REVEL	Uncertain	0.48
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0080	D
Polyphen		0.99	D
Vest4		0.53
MutPred		0.48		Gain of catalytic residue at G10 (P = 0.017)
MVP		0.80
MPC		0.86
ClinPred		0.93	D
GERP RS		3.1
PromoterAI		-0.10	Neutral
Varity_R		0.42
gMVP		0.68
Mutation Taster		=59/41	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs142954960; hg19: chr5-1201794;