3-94015069-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001001850.3(STX19):c.201T>A(p.Asn67Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000231 in 1,613,788 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00024 ( 0 hom. )

Consequence

STX19
NM_001001850.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.251

Variant links:

Genes affected

STX19 (HGNC:19300): (syntaxin 19) Predicted to enable SNAP receptor activity and SNARE binding activity. Predicted to be involved in intracellular protein transport; synaptic vesicle fusion to presynaptic active zone membrane; and vesicle docking. Predicted to be part of SNARE complex. Predicted to be active in presynaptic active zone membrane and synaptic vesicle. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

STX19 links:

ARL13B (HGNC:25419): (ADP ribosylation factor like GTPase 13B) This gene encodes a member of the ADP-ribosylation factor-like family. The encoded protein is a small GTPase that contains both N-terminal and C-terminal guanine nucleotide-binding motifs. This protein is localized in the cilia and plays a role in cilia formation and in maintenance of cilia. Mutations in this gene are the cause of Joubert syndrome 8. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Mar 2010]

ARL13B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.11541349).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STX19	NM_001001850.3 linkuse as main transcript	c.201T>A	p.Asn67Lys	missense_variant	2/2	ENST00000315099.3
ARL13B	NM_001174150.2 linkuse as main transcript	c.380+11161A>T		intron_variant		ENST00000394222.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STX19	ENST00000315099.3 linkuse as main transcript	c.201T>A	p.Asn67Lys	missense_variant	2/2	1	NM_001001850.3	P1
ARL13B	ENST00000394222.8 linkuse as main transcript	c.380+11161A>T		intron_variant		1	NM_001174150.2	P1	Q3SXY8-1

Frequencies

GnomAD3 genomes

AF:

0.000145

AC:

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000279

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000116

AC:

AN:

250916

Hom.:

AF XY:

0.000103

AC XY:

AN XY:

135676

show subpopulations

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000256

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000239

AC:

350

AN:

1461630

Hom.:

Cov.:

AF XY:

0.000245

AC XY:

178

AN XY:

727116

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000294

Gnomad4 OTH exome

AF:

0.000364

GnomAD4 genome

AF:

0.000145

AC:

AN:

152158

Hom.:

Cov.:

AF XY:

0.000135

AC XY:

AN XY:

74330

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000279

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000288

Hom.:

Bravo

AF:

0.000147

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.0000988

AC:

EpiCase

AF:

0.000382

EpiControl

AF:

0.000237

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 05, 2022

The c.201T>A (p.N67K) alteration is located in exon 2 (coding exon 1) of the STX19 gene. This alteration results from a T to A substitution at nucleotide position 201, causing the asparagine (N) at amino acid position 67 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.77

Cadd

Benign

Dann

Uncertain

0.98

DEOGEN2

Benign

0.022

Eigen

Benign

-0.75

Eigen_PC

Benign

-0.58

FATHMM_MKL

Benign

0.71

LIST_S2

Benign

0.72

M_CAP

Benign

0.0077

MetaRNN

Benign

0.12

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.69

MutationTaster

Benign

1.0

D;D;D;D;D;N

PrimateAI

Benign

0.28

PROVEAN

Benign

-1.1

REVEL

Benign

0.046

Sift

Uncertain

0.0090

Sift4G

Uncertain

0.030

Polyphen

0.011

Vest4

0.21

MutPred

0.49

Gain of ubiquitination at N67 (P = 0.0121);

MVP

0.43

MPC

0.0094

ClinPred

0.077

GERP RS

1.9

Varity_R

0.073

gMVP

0.28

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