11-61556190-C-A

Variant names:

• chr11-61556190-C-A
• rs147650793
• NM_001365809.2:c.49G>T

Variant summary

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

The NM_001365809.2(SYT7):​c.49G>T​(p.Val17Phe) variant causes a missense change. The variant allele was found at a frequency of 0.0000144 in 1,461,390 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V17I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: SYT7 NM_001365809.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.97

Genes affected

SYT7 (HGNC:11514): (synaptotagmin 7) This gene is a member of the synaptotagmin gene family and encodes a protein similar to other family members that mediate calcium-dependent regulation of membrane trafficking in synaptic transmission. A similar protein in rodents mediates hormone secretion and lysosome exocytosis. In humans, expression of this gene has been associated with prostate cancer. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Oct 2011]

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 rank	MANE	Protein	UniProt
SYT7	NM_001365809.2	c.49G>T	p.Val17Phe	missense_variant	Exon 2 of 13	ENST00000539008.6	NP_001352738.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYT7	ENST00000539008.6	c.49G>T	p.Val17Phe	missense_variant	Exon 2 of 13	5	NM_001365809.2	ENSP00000439694.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.0000144 AC: 21 AN: 1461390 Hom.: 0 Cov.: 31 AF XY: 0.0000124 AC XY: 9 AN XY: 726962

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000189

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 26, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.49G>T (p.V17F) alteration is located in exon 2 (coding exon 2) of the SYT7 gene. This alteration results from a G to T substitution at nucleotide position 49, causing the valine (V) at amino acid position 17 to be replaced by a phenylalanine (F). 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	0.14
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.040
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.18	T;.;.;.;.;.;.
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.94	D;D;D;D;D;D;D
M_CAP	Benign	0.077	D
MetaRNN	Uncertain	0.55	D;D;D;D;D;D;D
MetaSVM	Uncertain	-0.26	T
MutationAssessor	Benign	2.0	M;M;M;M;M;M;.
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-1.7	N;N;N;N;N;N;D
REVEL	Benign	0.22
Sift	Pathogenic	0.0	D;D;D;D;D;D;D
Sift4G	Uncertain	0.0070	D;D;D;D;D;D;.
Polyphen		1.0	D;.;.;.;.;.;.
Vest4		0.73
MutPred		0.41		Gain of sheet (P = 0.0149);Gain of sheet (P = 0.0149);Gain of sheet (P = 0.0149);Gain of sheet (P = 0.0149);Gain of sheet (P = 0.0149);Gain of sheet (P = 0.0149);Gain of sheet (P = 0.0149);
MVP		0.79
MPC		1.2
ClinPred		0.96	D
GERP RS		4.9
Varity_R		0.49
gMVP		0.79

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

LitVar

Other links and lift over

dbSNP: rs147650793; hg19: chr11-61323662;