Genetic Variant SYT7:p.Arg238Gln (chr11-61542439-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001365809.2(SYT7):c.713G>A(p.Arg238Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0113 in 1,532,704 control chromosomes in the GnomAD database, including 126 homozygotes. In-silico tool predicts a benign outcome for this variant. 10/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0069 ( 6 hom., cov: 33)

Exomes 𝑓: 0.012 ( 120 hom. )

Consequence

SYT7
NM_001365809.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.25

Variant links:

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]

SYT7 links:

ENSG00000256443 (HGNC:):

ENSG00000256443 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0058818758).

BP6

Variant 11-61542439-C-T is Benign according to our data. Variant chr11-61542439-C-T is described in ClinVar as [Benign]. Clinvar id is 2641831.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYT7	NM_001365809.2 link	c.713G>A	p.Arg238Gln	missense_variant	Exon 6 of 13	ENST00000539008.6	NP_001352738.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYT7	ENST00000539008.6 link	c.713G>A	p.Arg238Gln	missense_variant	Exon 6 of 13	5	NM_001365809.2	ENSP00000439694.1		O43581-3

Frequencies

GnomAD3 genomes

AF:

0.00693

AC:

1054

AN:

152126

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00246

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.00249

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00228

Gnomad FIN

AF:

0.00678

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0121

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00557

AC:

727

AN:

130558

Hom.:

AF XY:

0.00568

AC XY:

406

AN XY:

71426

show subpopulations

Gnomad AFR exome

AF:

0.00163

Gnomad AMR exome

AF:

0.00169

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00197

Gnomad FIN exome

AF:

0.00690

Gnomad NFE exome

AF:

0.0117

Gnomad OTH exome

AF:

0.00322

GnomAD4 exome

AF:

0.0118

AC:

16247

AN:

1380460

Hom.:

120

Cov.:

AF XY:

0.0113

AC XY:

7694

AN XY:

681122

show subpopulations

Gnomad4 AFR exome

AF:

0.00178

Gnomad4 AMR exome

AF:

0.00177

Gnomad4 ASJ exome

AF:

0.0000398

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00194

Gnomad4 FIN exome

AF:

0.00759

Gnomad4 NFE exome

AF:

0.0141

Gnomad4 OTH exome

AF:

0.00914

GnomAD4 genome

AF:

0.00692

AC:

1054

AN:

152244

Hom.:

Cov.:

AF XY:

0.00634

AC XY:

472

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.00245

Gnomad4 AMR

AF:

0.00248

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00228

Gnomad4 FIN

AF:

0.00678

Gnomad4 NFE

AF:

0.0121

Gnomad4 OTH

AF:

0.00236

Alfa

AF:

0.00337

Hom.:

Bravo

AF:

0.00642

TwinsUK

AF:

0.0162

AC:

ALSPAC

AF:

0.0143

AC:

ExAC

AF:

0.00312

AC:

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Feb 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

SYT7: BP4, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.60

CADD

Uncertain

DANN

Uncertain

1.0

Eigen

Benign

0.062

Eigen_PC

Benign

0.084

FATHMM_MKL

Benign

0.50

LIST_S2

Benign

0.78

T;T

MetaRNN

Benign

0.0059

T;T

MetaSVM

Benign

-0.98

PROVEAN

Benign

-0.26

N;N

REVEL

Benign

0.047

Sift

Benign

0.036

D;T

Sift4G

Benign

0.26

T;T

Vest4

0.12

MVP

0.27

ClinPred

0.019

GERP RS

2.9

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over