STX7 p.Gln53His

Variant names:

• chr6-132472372-T-A
• NM_003569.3:c.159A>T
• STX7 p.Gln53His

Your query was ambiguous. Multiple possible variants found:

• chr6-132472372-T-A
• chr6-132472372-T-G

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 7P and 1B. PS1 PM2 PP2 BP4

The NM_003569.3(STX7):​c.159A>T​(p.Gln53His) 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. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely pathogenic in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: STX7 NM_003569.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.325
• Publications: 0 publications found

Genes affected

STX7 (HGNC:11442): (syntaxin 7) The protein encoded by this gene is a syntaxin family membrane receptor involved in vesicle transport. The encoded protein binds alpha-SNAP, an important regulator of transport vesicle fusion. Along with syntaxin 13, this protein plays a role in the ordered fusion of endosomes and lysosomes with the phagosome. [provided by RefSeq, May 2016]

ACMG classification

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PS1: Transcript NM_003569.3 (STX7) is affected with MISSENSE_VARIANT having same AA change as one Pathogenic present in ClinVar.
• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 1 curated pathogenic missense variants (we use a threshold of 10). The gene has 0 curated benign missense variants. Gene score misZ: 0.81095 (below the threshold of 3.09). Trascript score misZ: 0.47494 (below the threshold of 3.09).
• BP4: Computational evidence support a benign effect (MetaRNN=0.42072383).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003569.3. 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
	STX7	NM_003569.3	MANE Select	c.159A>T	p.Gln53His	missense	Exon 4 of 10	NP_003560.2	O15400-1
	STX7	NM_001326578.2		c.159A>T	p.Gln53His	missense	Exon 4 of 10	NP_001313507.1	O15400-1
	STX7	NM_001326579.2		c.159A>T	p.Gln53His	missense	Exon 4 of 10	NP_001313508.1	O15400-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STX7	ENST00000367941.7	TSL:1 MANE Select	c.159A>T	p.Gln53His	missense	Exon 4 of 10	ENSP00000356918.1	O15400-1
	STX7	ENST00000862289.1		c.159A>T	p.Gln53His	missense	Exon 4 of 10	ENSP00000532348.1
	STX7	ENST00000862290.1		c.159A>T	p.Gln53His	missense	Exon 4 of 10	ENSP00000532349.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.36
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	17
DANN	Uncertain	0.97
DEOGEN2	Benign	0.077	T
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.64
FATHMM_MKL	Benign	0.75	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.42	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.84	L
PhyloP100		-0.33
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	0.27	N
REVEL	Benign	0.22
Sift	Benign	0.78	T
Sift4G	Benign	0.75	T
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.12
gMVP		0.30
Mutation Taster		=27/73	disease causing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr6-132793511;