11-61528139-C-A

Variant names:

• chr11-61528139-C-A
• rs374646904
• NM_001365809.2:c.1247G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001365809.2(SYT7):​c.1247G>T​(p.Arg416Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 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. R416Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SYT7 NM_001365809.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.80
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26145878).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001365809.2. 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
	SYT7	NM_001365809.2	MANE Select	c.1247G>T	p.Arg416Leu	missense	Exon 9 of 13	NP_001352738.1	O43581-3
	SYT7	NM_001411007.1		c.755G>T	p.Arg252Leu	missense	Exon 7 of 11	NP_001397936.1	O43581-5
	SYT7	NM_001370210.1		c.686G>T	p.Arg229Leu	missense	Exon 3 of 6	NP_001357139.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYT7	ENST00000539008.6	TSL:5 MANE Select	c.1247G>T	p.Arg416Leu	missense	Exon 9 of 13	ENSP00000439694.1	O43581-3
	SYT7	ENST00000540677.5	TSL:1	c.623G>T	p.Arg208Leu	missense	Exon 6 of 10	ENSP00000444201.1	O43581-2
	SYT7	ENST00000263846.8	TSL:1	c.398G>T	p.Arg133Leu	missense	Exon 5 of 9	ENSP00000263846.4	O43581-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.079	T
BayesDel_noAF	Benign	-0.35
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Benign	0.21	T
Eigen	Benign	-0.032
Eigen_PC	Benign	0.14
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.0089	T
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L
PhyloP100		3.8
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.17
Sift	Benign	0.20	T
Sift4G	Benign	0.30	T
Polyphen		0.025	B
Vest4		0.27
MVP		0.20
MPC		1.3
ClinPred		0.87	D
GERP RS		4.4
Varity_R		0.24
gMVP		0.47
Mutation Taster		=52/48	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs374646904; hg19: chr11-61295611;