Genetic Variant STX12:p.Thr93Asn (chr1-27793622-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_177424.3(STX12):c.278C>A(p.Thr93Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000026 in 1,461,196 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.000026 ( 0 hom. )

Consequence

STX12
NM_177424.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.71

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.17607445).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_177424.3. 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
	STX12	NM_177424.3	MANE Select	c.278C>A	p.Thr93Asn	missense	Exon 3 of 9	NP_803173.1	Q86Y82

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
STX12	ENST00000373943.9	TSL:1 MANE Select	c.278C>A	p.Thr93Asn	missense	Exon 3 of 9	ENSP00000363054.4	Q86Y82
STX12	ENST00000961042.1		c.278C>A	p.Thr93Asn	missense	Exon 3 of 9	ENSP00000631101.1
STX12	ENST00000893601.1		c.278C>A	p.Thr93Asn	missense	Exon 3 of 9	ENSP00000563660.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000159

AC:

AN:

251300

AF XY:

0.0000221

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000579

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000260

AC:

AN:

1461196

Hom.:

Cov.:

AF XY:

0.0000303

AC XY:

AN XY:

726962

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33458

American (AMR)

AF:

0.0000224

AC:

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26124

East Asian (EAS)

AF:

0.00

AC:

AN:

39676

South Asian (SAS)

AF:

0.00

AC:

AN:

86246

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53382

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000315

AC:

AN:

1111446

Other (OTH)

AF:

0.0000331

AC:

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.459

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000413

Hom.:

Bravo

AF:

0.0000113

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.63

CADD

Uncertain

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.019

Eigen

Benign

-0.12

Eigen_PC

Benign

0.035

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.89

M_CAP

Benign

0.0060

MetaRNN

Benign

0.18

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

PhyloP100

5.7

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.67

REVEL

Benign

0.076

Sift

Benign

0.27

Sift4G

Benign

0.52

Polyphen

0.043

Vest4

0.11

MVP

0.30

MPC

0.40

ClinPred

0.26

GERP RS

3.6

Varity_R

0.073

gMVP

0.11

Mutation Taster

=74/26

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over