Variant chr6-132503517-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_003569.3(STX7):c.14C>T(p.Pro5Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000366 in 1,613,786 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000038 ( 0 hom. )

Consequence

STX7
NM_003569.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.82

Variant links:

Genes affected

STX7 (HGNC:11442): (syntaxin 7) The protein encoded by this gene is a syntaxin family membrane receptor involved in vesicle transport. The encoded protein binds alpha-SNAP, an important regulator of transport vesicle fusion. Along with syntaxin 13, this protein plays a role in the ordered fusion of endosomes and lysosomes with the phagosome. [provided by RefSeq, May 2016]

STX7 links:

STX7 (HGNC:):

STX7 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STX7	NM_003569.3 linkuse as main transcript	c.14C>T	p.Pro5Leu	missense_variant	2/10	ENST00000367941.7	NP_003560.2	O15400-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
STX7	ENST00000367941.7 linkuse as main transcript	c.14C>T	p.Pro5Leu	missense_variant	2/10	1	NM_003569.3	ENSP00000356918.1	O15400-1
STX7	ENST00000367937.4 linkuse as main transcript	c.14C>T	p.Pro5Leu	missense_variant	2/10	5		ENSP00000356914.4	O15400-2
STX7	ENST00000475879.1 linkuse as main transcript	n.131C>T		non_coding_transcript_exon_variant	2/3	2
STX7	ENST00000448348.3 linkuse as main transcript	n.79-3C>T		splice_region_variant, intron_variant		4

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000119

AC:

AN:

251112

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135754

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:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000383

AC:

AN:

1461578

Hom.:

Cov.:

AF XY:

0.0000371

AC XY:

AN XY:

727122

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000928

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000414

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152208

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

EpiCase

AF:

0.0000546

EpiControl

AF:

0.0000593

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

Aug 04, 2023

The c.14C>T (p.P5L) alteration is located in exon 2 (coding exon 1) of the STX7 gene. This alteration results from a C to T substitution at nucleotide position 14, causing the proline (P) at amino acid position 5 to be replaced by a leucine (L). 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

-0.24

BayesDel_noAF

Benign

-0.48

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.11

T;.

Eigen

Benign

-0.22

Eigen_PC

Benign

-0.073

FATHMM_MKL

Uncertain

0.82

LIST_S2

Uncertain

0.87

D;D

M_CAP

Benign

0.0096

MetaRNN

Benign

0.15

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

L;L

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-1.3

N;N

REVEL

Benign

0.026

Sift

Uncertain

0.026

D;T

Sift4G

Benign

0.40

T;T

Polyphen

0.036

B;.

Vest4

0.15

MutPred

0.37

Loss of disorder (P = 0.0411);Loss of disorder (P = 0.0411);

MVP

0.60

MPC

0.15

ClinPred

0.20

GERP RS

3.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.036

gMVP

0.27

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.28

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.28

Position offset: -3

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