19-13145391-A-G

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_003765.3(STX10):c.368T>C(p.Leu123Pro) variant causes a missense change. The variant allele was found at a frequency of 0.0000106 in 1,610,086 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 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

STX10
NM_003765.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.84

Publications

0 publications found

Variant links:

Genes affected

STX10 (HGNC:11428): (syntaxin 10) This gene belongs to the syntaxin family and encodes a soluble N-ethylmaleimide sensitive factor attachment protein receptor (SNARE). The encoded protein is involved in docking and fusion events at the Golgi apparatus. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2012]

STX10 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.33638972).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STX10	NM_003765.3 link	c.368T>C	p.Leu123Pro	missense_variant	Exon 5 of 8	ENST00000587230.6	NP_003756.1	O60499-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
STX10	ENST00000587230.6 link	c.368T>C	p.Leu123Pro	missense_variant	Exon 5 of 8	1	NM_003765.3	ENSP00000466298.1	O60499-1
STX10	ENST00000589083.5 link	c.368T>C	p.Leu123Pro	missense_variant	Exon 5 of 7	1		ENSP00000465398.1	Q5U8S2
STX10	ENST00000587318.5 link	c.320T>C	p.Leu107Pro	missense_variant	Exon 4 of 7	2		ENSP00000464943.1	K7EIY4
STX10	ENST00000242770.9 link	c.368T>C	p.Leu123Pro	missense_variant	Exon 5 of 8	1		ENSP00000242770.5	X6R2W0
STX10	ENST00000593126.5 link	c.275T>C	p.Leu92Pro	missense_variant	Exon 4 of 7	3		ENSP00000466272.1	K7ELY2
STX10	ENST00000591197.1 link	c.86T>C	p.Leu29Pro	missense_variant	Exon 4 of 4	3		ENSP00000464970.1	K7EJ05
STX10	ENST00000440593.3 link	n.*157T>C		non_coding_transcript_exon_variant	Exon 5 of 7	5		ENSP00000415176.3	F6RTM7
STX10	ENST00000440593.3 link	n.*157T>C		3_prime_UTR_variant	Exon 5 of 7	5		ENSP00000415176.3	F6RTM7
STX10	ENST00000343587.9 link	c.227-6T>C		splice_region_variant, intron_variant	Intron 3 of 6	1		ENSP00000339350.4	O60499-2

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000202

AC:

AN:

247462

AF XY:

0.00000745

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000443

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000103

AC:

AN:

1457894

Hom.:

Cov.:

AF XY:

0.00000414

AC XY:

AN XY:

725470

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33476

American (AMR)

AF:

0.00

AC:

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.00

AC:

AN:

86236

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49736

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0000117

AC:

AN:

1111788

Other (OTH)

AF:

0.0000331

AC:

AN:

60352

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

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

AF:

0.0000131

AC:

AN:

152192

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41448

American (AMR)

AF:

0.00

AC:

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5198

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68032

Other (OTH)

AF:

0.00

AC:

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000344

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 02, 2022

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.368T>C (p.L123P) alteration is located in exon 5 (coding exon 5) of the STX10 gene. This alteration results from a T to C substitution at nucleotide position 368, causing the leucine (L) at amino acid position 123 to be replaced by a proline (P). 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

0.075

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.24

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.15

.;T;T;T;T;T

Eigen

Benign

-0.064

Eigen_PC

Benign

-0.25

FATHMM_MKL

Benign

0.37

LIST_S2

Benign

0.49

T;T;T;T;T;T

M_CAP

Benign

0.014

MetaRNN

Benign

0.34

T;T;T;T;T;T

MetaSVM

Benign

-0.43

MutationAssessor

Uncertain

2.4

.;.;M;.;.;.

PhyloP100

3.8

PrimateAI

Uncertain

0.54

PROVEAN

Uncertain

-2.6

D;.;.;.;.;.

REVEL

Benign

0.26

Sift

Uncertain

0.0010

D;.;.;.;.;.

Sift4G

Uncertain

0.0030

D;D;D;D;.;D

Polyphen

1.0, 0.88

.;D;P;.;.;.

Vest4

0.60

MutPred

0.42

Gain of disorder (P = 0.0151);Gain of disorder (P = 0.0151);Gain of disorder (P = 0.0151);.;.;.;

MVP

0.71

MPC

1.2

ClinPred

0.69

GERP RS

3.3

PromoterAI

-0.0085

Neutral

(source)

Varity_R

0.48

gMVP

0.74

Mutation Taster

=73/27

polymorphism

(source)

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

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over