rs193920742

Positions:

• chr17-9505052-T-G

Variant summary

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

The NM_004853.3(STX8):​c.434A>C​(p.Gln145Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 30)
• Consequence: STX8 NM_004853.3 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 3.87

Genes affected

STX8 (HGNC:11443): (syntaxin 8) The gene is a member of the syntaxin family. The encoded protein is involved in protein trafficking from early to late endosomes via vesicle fusion and exocytosis. A related pseudogene has been identified on chromosome 12. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2010]

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
STX8	NM_004853.3	c.434A>C	p.Gln145Pro	missense_variant	5/8	ENST00000306357.9	NP_004844.1
STX8	XM_011524079.2	c.269A>C	p.Gln90Pro	missense_variant	3/6		XP_011522381.1
STX8	NR_033656.2	n.240A>C		non_coding_transcript_exon_variant	3/6
STX8	XR_934120.3	n.446A>C		non_coding_transcript_exon_variant	5/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STX8	ENST00000306357.9	c.434A>C	p.Gln145Pro	missense_variant	5/8	1	NM_004853.3	ENSP00000305255	P1
STX8	ENST00000574431.5	c.101A>C	p.Gln34Pro	missense_variant	4/7	3		ENSP00000467749
STX8	ENST00000575294.6	c.118-13131A>C		intron_variant, NMD_transcript_variant		5		ENSP00000468093
STX8	ENST00000575858.5	c.*93A>C		3_prime_UTR_variant, NMD_transcript_variant	3/6	3		ENSP00000460355

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 30

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Malignant tumor of prostate Uncertain:1

Uncertain significance, no assertion criteria provided

literature only

Science for Life laboratory, Karolinska Institutet

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.89
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.52	D;.
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.89	D;D
M_CAP	Benign	0.018	T
MetaRNN	Uncertain	0.54	D;D
MetaSVM	Benign	-0.33	T
MutationAssessor	Pathogenic	3.1	M;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.61	T
PROVEAN	Uncertain	-2.6	D;.
REVEL	Benign	0.23
Sift	Benign	0.090	T;.
Sift4G	Benign	0.17	T;D
Polyphen		0.94	P;.
Vest4		0.59
MutPred		0.38		Gain of glycosylation at K146 (P = 0.1163);.;
MVP		0.61
MPC		0.19
ClinPred		0.97	D
GERP RS		5.7
Varity_R		0.63
gMVP		0.85

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: rs193920742; hg19: chr17-9408369; COSMIC: COSV60496975; COSMIC: COSV60496975;