chr6-132472372-T-G

Variant names:

• chr6-132472372-T-G
• rs864309676
• NM_003569.3:c.159A>C

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP2 PP5

The NM_003569.3(STX7):​c.159A>C​(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. Variant has been reported in ClinVar as Likely pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: STX7 NM_003569.3 missense
• Clinical Significance: Likely pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: -0.325
• Publications: 1 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: Uncertain_significance. The variant received 4 ACMG points.

• 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).
• PP5: Variant 6-132472372-T-G is Pathogenic according to our data. Variant chr6-132472372-T-G is described in ClinVar as Likely_pathogenic. ClinVar VariationId is 218904.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STX7	NM_003569.3	c.159A>C	p.Gln53His	missense_variant	Exon 4 of 10	ENST00000367941.7	NP_003560.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STX7	ENST00000367941.7	c.159A>C	p.Gln53His	missense_variant	Exon 4 of 10	1	NM_003569.3	ENSP00000356918.1
STX7	ENST00000367937.4	c.159A>C	p.Gln53His	missense_variant	Exon 4 of 10	5		ENSP00000356914.4
STX7	ENST00000448348.3	n.221A>C		non_coding_transcript_exon_variant	Exon 4 of 7	4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Abnormality of neuronal migration Pathogenic:1

Oct 31, 2014

Génétique et pathophysiologie de maladies neurodéveloppementales et épileptogènes, Institut de génétique et de biologie moléculaire et cellulaire

Significance: Likely pathogenic

Review Status: no assertion criteria provided

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.36
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.077	T;.
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.64
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Uncertain	0.91	D;D
M_CAP	Benign	0.023	T
MetaRNN	Uncertain	0.43	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.84	L;L
PhyloP100		-0.33
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	0.27	N;N
REVEL	Benign	0.22
Sift	Benign	0.78	T;T
Sift4G	Benign	0.75	T;T
Polyphen		0.26	B;.
Vest4		0.79
MutPred		0.41		Loss of MoRF binding (P = 0.1725);Loss of MoRF binding (P = 0.1725);
MVP		0.52
MPC		0.61
ClinPred		0.82	D
GERP RS		-1.8
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 (ClinVar)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs864309676; hg19: chr6-132793511;