Variant chr1-27812172-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_177424.3(STX12):c.480G>C(p.Glu160Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000276 in 1,555,954 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 0.000026 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000028 ( 0 hom. )

Consequence

STX12
NM_177424.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.32

Variant links:

Genes affected

STX12 (HGNC:11430): (syntaxin 12) Predicted to enable SNAP receptor activity and SNARE binding activity. Involved in autophagosome assembly; cholesterol efflux; and protein stabilization. Located in several cellular components, including membrane raft; phagocytic vesicle; and phagophore assembly site. Part of SNARE complex. Colocalizes with BLOC-1 complex. [provided by Alliance of Genome Resources, Apr 2022]

STX12 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.027933568).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STX12	NM_177424.3 linkuse as main transcript	c.480G>C	p.Glu160Asp	missense_variant	6/9	ENST00000373943.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
STX12	ENST00000373943.9 linkuse as main transcript	c.480G>C	p.Glu160Asp	missense_variant	6/9	1	NM_177424.3	P1
STX12	ENST00000440806.2 linkuse as main transcript	c.549G>C	p.Glu183Asp	missense_variant	7/7	3
STX12	ENST00000472285.1 linkuse as main transcript	n.53G>C		non_coding_transcript_exon_variant	2/3	3
STX12	ENST00000481874.1 linkuse as main transcript	n.377G>C		non_coding_transcript_exon_variant	2/2	5

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152198

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:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000599

AC:

AN:

166902

Hom.:

AF XY:

0.0000114

AC XY:

AN XY:

87832

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:

0.0000434

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000278

AC:

AN:

1403756

Hom.:

Cov.:

AF XY:

0.0000318

AC XY:

AN XY:

692756

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:

0.0000126

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000352

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152198

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74354

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:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000108

Hom.:

Bravo

AF:

0.0000227

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

Oct 06, 2021

The c.480G>C (p.E160D) alteration is located in exon 6 (coding exon 6) of the STX12 gene. This alteration results from a G to C substitution at nucleotide position 480, causing the glutamic acid (E) at amino acid position 160 to be replaced by an aspartic acid (D). 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

0.068

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.65

CADD

Benign

DANN

Benign

0.79

DEOGEN2

Benign

0.015

T;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.21

LIST_S2

Benign

0.70

T;T

M_CAP

Benign

0.0071

MetaRNN

Benign

0.028

T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

-1.6

N;.

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-0.23

N;N

REVEL

Benign

0.24

Sift

Benign

0.69

T;T

Sift4G

Benign

0.66

T;T

Polyphen

0.0

B;.

Vest4

0.14

MutPred

0.25

Loss of helix (P = 0.028);.;

MVP

0.19

MPC

0.26

ClinPred

0.032

GERP RS

-4.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.043

gMVP

0.18

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