11-7252236-C-A

Variant names:

• chr11-7252236-C-A
• rs749543472
• NM_175733.4:c.50C>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_175733.4(SYT9):​c.50C>A​(p.Ala17Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000741 in 1,349,158 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A17V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.4e-7 (0 hom.)
• Consequence: SYT9 NM_175733.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.48
• Publications: 0 publications found

Genes affected

SYT9 (HGNC:19265): (synaptotagmin 9) Predicted to enable several functions, including calcium ion binding activity; phospholipid binding activity; and syntaxin binding activity. Predicted to be involved in calcium-ion regulated exocytosis; cellular response to calcium ion; and regulation of secretion by cell. Predicted to be located in clathrin-coated endocytic vesicle membrane. Predicted to be active in hippocampal mossy fiber to CA3 synapse; plasma membrane; and secretory vesicle. Predicted to be integral component of synaptic vesicle membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_175733.4. 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
	SYT9	NM_175733.4	MANE Select	c.50C>A	p.Ala17Asp	missense	Exon 1 of 7	NP_783860.1	Q86SS6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYT9	ENST00000318881.11	TSL:1 MANE Select	c.50C>A	p.Ala17Asp	missense	Exon 1 of 7	ENSP00000324419.6	Q86SS6
	SYT9	ENST00000532592.1	TSL:2	n.50C>A		non_coding_transcript_exon	Exon 1 of 6	ENSP00000434558.1	B3KNT7
	SYT9	ENST00000524820.6	TSL:2	n.49+13320C>A		intron	N/A	ENSP00000432141.2	E9PDN4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00 AC: 0 AN: 103928 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.41e-7 AC: 1 AN: 1349158 Hom.: 0 Cov.: 30 AF XY: 0.00000150 AC XY: 1 AN XY: 664514

African (AFR) AF: 0.00 AC: 0 AN: 27296

American (AMR) AF: 0.00 AC: 0 AN: 29040

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23732

East Asian (EAS) AF: 0.00 AC: 0 AN: 29540

South Asian (SAS) AF: 0.00 AC: 0 AN: 74290

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46834

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4712

European-Non Finnish (NFE) AF: 9.45e-7 AC: 1 AN: 1057796

Other (OTH) AF: 0.00 AC: 0 AN: 55918

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.39
BayesDel_addAF	Benign	-0.089	T
BayesDel_noAF	Benign	-0.36
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.027	T
Eigen	Benign	-0.056
Eigen_PC	Benign	0.053
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.79	T
M_CAP	Pathogenic	0.90	D
MetaRNN	Uncertain	0.44	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.7	L
PhyloP100		3.5
PrimateAI	Pathogenic	0.93	D
PROVEAN	Benign	-0.77	N
REVEL	Benign	0.044
Sift	Uncertain	0.024	D
Sift4G	Benign	0.48	T
Polyphen		0.26	B
Vest4		0.48
MutPred		0.35		Gain of disorder (P = 0.0663)
MVP		0.76
MPC		0.76
ClinPred		0.69	D
GERP RS		3.8
PromoterAI		-0.0088	Neutral
Varity_R		0.46
gMVP		0.57
Mutation Taster		=33/67	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

Other links and lift over

dbSNP: rs749543472; hg19: chr11-7273467;