Genetic Variant SYT7:p.Arg238Pro (chr11-61542439-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001365809.2(SYT7):c.713G>C(p.Arg238Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000724 in 1,380,462 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/17 in silico tools predict 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. R238Q) has been classified as Benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

SYT7
NM_001365809.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.25

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

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=0.2024566).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SYT7	NM_001365809.2	MANE Select	c.713G>C	p.Arg238Pro	missense	Exon 6 of 13	NP_001352738.1	O43581-3
SYT7	NM_001370210.1		c.275G>C	p.Arg92Pro	missense	Exon 1 of 6	NP_001357139.1
SYT7	NM_001411007.1		c.572+3592G>C		intron	N/A	NP_001397936.1	O43581-5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SYT7	ENST00000539008.6	TSL:5 MANE Select	c.713G>C	p.Arg238Pro	missense	Exon 6 of 13	ENSP00000439694.1	O43581-3
SYT7	ENST00000540677.5	TSL:1	c.440+3592G>C		intron	N/A	ENSP00000444201.1	O43581-2
SYT7	ENST00000263846.8	TSL:1	c.215+8945G>C		intron	N/A	ENSP00000263846.4	O43581-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.24e-7

AC:

AN:

1380462

Hom.:

Cov.:

AF XY:

0.00000147

AC XY:

AN XY:

681124

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31438

American (AMR)

AF:

0.00

AC:

AN:

35618

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25100

East Asian (EAS)

AF:

0.00

AC:

AN:

35688

South Asian (SAS)

AF:

0.0000127

AC:

AN:

79034

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4254

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1078042

Other (OTH)

AF:

0.00

AC:

AN:

57674

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.54

CADD

Benign

(source)

DANN

Benign

0.97

Eigen

Benign

0.062

Eigen_PC

Benign

0.084

FATHMM_MKL

Uncertain

0.77

LIST_S2

Benign

0.72

M_CAP

Pathogenic

0.39

MetaRNN

Benign

0.20

MetaSVM

Benign

-0.96

PhyloP100

1.3

PROVEAN

Benign

-0.41

REVEL

Benign

0.037

Sift

Benign

0.030

Sift4G

Benign

0.22

Vest4

0.15

MutPred

0.41

Loss of MoRF binding (P = 0.0039)

MVP

0.30

ClinPred

0.22

GERP RS

2.9

Mutation Taster

=72/28

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over