chr11-59755628-T-C

Position:

• chr11-59755628-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004177.5(STX3):​c.23T>C​(p.Leu8Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000694 in 1,441,912 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: STX3 NM_004177.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0430

Genes affected

STX3 (HGNC:11438): (syntaxin 3) The gene is a member of the syntaxin family. The encoded protein is targeted to the apical membrane of epithelial cells where it forms clusters and is important in establishing and maintaining polarity necessary for protein trafficking involving vesicle fusion and exocytosis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2010]

STX3 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25031376).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STX3	NM_004177.5	c.23T>C	p.Leu8Pro	missense_variant	1/11	ENST00000337979.9	NP_004168.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STX3	ENST00000337979.9	c.23T>C	p.Leu8Pro	missense_variant	1/11	1	NM_004177.5	ENSP00000338562.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.94e-7 AC: 1 AN: 1441912 Hom.: 0 Cov.: 31 AF XY: 0.00000139 AC XY: 1 AN XY: 717984

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.02e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 14, 2024

The c.23T>C (p.L8P) alteration is located in exon 1 (coding exon 1) of the STX3 gene. This alteration results from a T to C substitution at nucleotide position 23, causing the leucine (L) at amino acid position 8 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	0.99
BayesDel_addAF	Benign	-0.035	T
BayesDel_noAF	Benign	-0.29
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.35	T;.;.
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.17
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.78	T;T;T
M_CAP	Pathogenic	0.47	D
MetaRNN	Benign	0.25	T;T;T
MetaSVM	Benign	-0.84	T
MutationAssessor	Uncertain	2.4	M;.;M
PrimateAI	Pathogenic	0.83	D
PROVEAN	Uncertain	-3.6	D;.;D
REVEL	Benign	0.21
Sift	Uncertain	0.0070	D;.;D
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		0.96	D;.;.
Vest4		0.33
MutPred		0.62		Loss of stability (P = 0.0466);Loss of stability (P = 0.0466);Loss of stability (P = 0.0466);
MVP		0.49
MPC		0.49
ClinPred		0.92	D
GERP RS		3.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.80
gMVP		0.84

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

Other links and lift over

dbSNP: rs1050352983; hg19: chr11-59523101;