7-73705197-A-C

Position:

• chr7-73705197-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_004603.4(STX1A):​c.236T>G​(p.Met79Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: STX1A NM_004603.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.743

Genes affected

STX1A (HGNC:11433): (syntaxin 1A) This gene encodes a member of the syntaxin superfamily. Syntaxins are nervous system-specific proteins implicated in the docking of synaptic vesicles with the presynaptic plasma membrane. Syntaxins possess a single C-terminal transmembrane domain, a SNARE [Soluble NSF (N-ethylmaleimide-sensitive fusion protein)-Attachment protein REceptor] domain (known as H3), and an N-terminal regulatory domain (Habc). Syntaxins bind synaptotagmin in a calcium-dependent fashion and interact with voltage dependent calcium and potassium channels via the C-terminal H3 domain. This gene product is a key molecule in ion channel regulation and synaptic exocytosis. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Sep 2009]

STX1A (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3413933).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STX1A	NM_004603.4	c.236T>G	p.Met79Arg	missense_variant	4/10	ENST00000222812.8	NP_004594.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STX1A	ENST00000222812.8	c.236T>G	p.Met79Arg	missense_variant	4/10	1	NM_004603.4	ENSP00000222812.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Seizure;C3714756:Intellectual disability Uncertain:1

Uncertain significance, criteria provided, single submitter

research

Institute of Human Genetics, University of Leipzig Medical Center

Apr 22, 2022

This variant was identified as de novo. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.91
BayesDel_addAF	Benign	0.0042	T
BayesDel_noAF	Benign	-0.23
CADD	Pathogenic	26
DANN	Benign	0.97
DEOGEN2	Uncertain	0.48	T;.;T;.
Eigen	Benign	0.022
Eigen_PC	Benign	0.11
FATHMM_MKL	Benign	0.76	D
LIST_S2	Uncertain	0.88	D;T;T;T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.34	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L;L;.;.
PrimateAI	Uncertain	0.70	T
PROVEAN	Uncertain	-2.6	D;N;N;N
REVEL	Benign	0.24
Sift	Benign	0.27	T;T;T;T
Sift4G	Benign	0.40	T;T;T;T
Polyphen		0.25	B;B;.;.
Vest4		0.49
MutPred		0.64		Loss of ubiquitination at K84 (P = 0.0526);Loss of ubiquitination at K84 (P = 0.0526);Loss of ubiquitination at K84 (P = 0.0526);Loss of ubiquitination at K84 (P = 0.0526);
MVP		0.39
MPC		1.6
ClinPred		0.90	D
GERP RS		4.7
Varity_R		0.79
gMVP		0.96

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-73119527;