Variant chr17-54999408-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_178509.6(STXBP4):c.244T>C(p.Ser82Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,460,990 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

STXBP4
NM_178509.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.38

Variant links:

Genes affected

STXBP4 (HGNC:19694): (syntaxin binding protein 4) Enables syntaxin binding activity. Involved in several processes, including positive regulation of cell cycle G1/S phase transition; positive regulation of keratinocyte proliferation; and protein stabilization. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

STXBP4 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.829

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STXBP4	NM_178509.6 linkuse as main transcript	c.244T>C	p.Ser82Pro	missense_variant	5/18	ENST00000376352.6	NP_848604.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STXBP4	ENST00000376352.6 linkuse as main transcript	c.244T>C	p.Ser82Pro	missense_variant	5/18	2	NM_178509.6	ENSP00000365530	P1	Q6ZWJ1-1
STXBP4	ENST00000434978.6 linkuse as main transcript	c.244T>C	p.Ser82Pro	missense_variant	5/17	1		ENSP00000391087
STXBP4	ENST00000398391.6 linkuse as main transcript	c.13T>C	p.Ser5Pro	missense_variant	4/11	1		ENSP00000381427		Q6ZWJ1-2
STXBP4	ENST00000405898.5 linkuse as main transcript	c.244T>C	p.Ser82Pro	missense_variant	4/11	5		ENSP00000385944

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000799

AC:

AN:

250446

Hom.:

AF XY:

0.00000739

AC XY:

AN XY:

135306

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1460990

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726728

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

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

Mar 07, 2024

The c.244T>C (p.S82P) alteration is located in exon 5 (coding exon 3) of the STXBP4 gene. This alteration results from a T to C substitution at nucleotide position 244, causing the serine (S) at amino acid position 82 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

Pathogenic

0.61

BayesDel_addAF

Benign

-0.086

BayesDel_noAF

Benign

-0.14

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.035

T;T;T;.

Eigen

Uncertain

0.27

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.92

D;D;D;T

M_CAP

Benign

0.048

MetaRNN

Pathogenic

0.83

D;D;D;D

MetaSVM

Benign

-0.75

MutationAssessor

Benign

1.9

L;.;.;.

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Uncertain

0.56

PROVEAN

Uncertain

-2.7

D;D;D;D

REVEL

Uncertain

0.37

Sift

Uncertain

0.0060

D;D;D;D

Sift4G

Uncertain

0.012

D;D;D;D

Polyphen

1.0

D;.;D;D

Vest4

0.80

MutPred

0.70

Loss of phosphorylation at S82 (P = 0.0823);Loss of phosphorylation at S82 (P = 0.0823);Loss of phosphorylation at S82 (P = 0.0823);.;

MVP

0.61

MPC

0.73

ClinPred

0.89

GERP RS

4.7

Varity_R

0.62

gMVP

0.78

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