6-132471597-G-C

Position:

• chr6-132471597-G-C

Variant summary

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

The NM_003569.3(STX7):​c.253C>G​(p.Gln85Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: STX7 NM_003569.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.20

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]

STX7 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STX7	NM_003569.3	c.253C>G	p.Gln85Glu	missense_variant	5/10	ENST00000367941.7	NP_003560.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STX7	ENST00000367941.7	c.253C>G	p.Gln85Glu	missense_variant	5/10	1	NM_003569.3	ENSP00000356918.1
STX7	ENST00000367937.4	c.253C>G	p.Gln85Glu	missense_variant	5/10	5		ENSP00000356914.4
STX7	ENST00000448348.3	n.315C>G		non_coding_transcript_exon_variant	5/7	4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 09, 2022

The c.253C>G (p.Q85E) alteration is located in exon 5 (coding exon 4) of the STX7 gene. This alteration results from a C to G substitution at nucleotide position 253, causing the glutamine (Q) at amino acid position 85 to be replaced by a glutamic acid (E). 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	Benign	0.21
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Uncertain	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	T;.
Eigen	Pathogenic	0.80
Eigen_PC	Pathogenic	0.82
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D;D
M_CAP	Benign	0.019	T
MetaRNN	Uncertain	0.61	D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	M;M
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-2.3	N;N
REVEL	Benign	0.27
Sift	Uncertain	0.0070	D;D
Sift4G	Benign	0.17	T;T
Polyphen		0.96	D;.
Vest4		0.65
MutPred		0.50		Gain of ubiquitination at K87 (P = 0.0316);Gain of ubiquitination at K87 (P = 0.0316);
MVP		0.88
MPC		0.66
ClinPred		0.89	D
GERP RS		5.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.53
gMVP		0.56

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-132792736;