Genetic Variant NM_001242394.2:c.635A>C (chr6-158718126-A-C) – 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_001242394.2(SYTL3):c.635A>C(p.His212Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000143 in 1,394,492 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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. H212R) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

SYTL3
NM_001242394.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.40

Publications

0 publications found

Variant links:

Genes affected

SYTL3 (HGNC:15587): (synaptotagmin like 3) The protein encoded by this gene belongs to a family of peripheral membrane proteins that play a role in vesicular trafficking. This protein binds phospholipids in the presence of calcium ions. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2016]

SYTL3 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=0.08032131).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYTL3	NM_001242394.2 link	c.635A>C	p.His212Pro	missense_variant	Exon 10 of 18	ENST00000611299.5	NP_001229323.1	Q4VX76-1B4E2A9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SYTL3	ENST00000611299.5 link	c.635A>C	p.His212Pro	missense_variant	Exon 10 of 18	5	NM_001242394.2	ENSP00000483936.1	Q4VX76-1
SYTL3	ENST00000360448.8 link	c.635A>C	p.His212Pro	missense_variant	Exon 11 of 19	5		ENSP00000353631.4	Q4VX76-1
SYTL3	ENST00000367081.7 link	c.517-7377A>C		intron_variant	Intron 8 of 15	5		ENSP00000356048.4	Q4VX76-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000143

AC:

AN:

1394492

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

687766

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31394

American (AMR)

AF:

0.00

AC:

AN:

35288

Ashkenazi Jewish (ASJ)

AF:

0.0000798

AC:

AN:

25074

East Asian (EAS)

AF:

0.00

AC:

AN:

35346

South Asian (SAS)

AF:

0.00

AC:

AN:

78634

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48088

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5678

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1077150

Other (OTH)

AF:

0.00

AC:

AN:

57840

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.47

CADD

Benign

9.3

(source)

DANN

Benign

0.90

DEOGEN2

Benign

0.0064

T;T;T

Eigen

Benign

-0.66

Eigen_PC

Benign

-0.62

FATHMM_MKL

Benign

0.24

LIST_S2

Benign

0.54

.;T;.

M_CAP

Benign

0.0051

MetaRNN

Benign

0.080

T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Uncertain

2.1

M;M;M

PhyloP100

1.4

PrimateAI

Benign

0.30

PROVEAN

Uncertain

-2.7

.;.;D

REVEL

Benign

0.044

Sift

Benign

0.27

.;.;T

Sift4G

Benign

0.28

T;T;T

Polyphen

0.040

B;B;B

Vest4

0.18

MutPred

0.30

Gain of glycosylation at H212 (P = 0.0894);Gain of glycosylation at H212 (P = 0.0894);Gain of glycosylation at H212 (P = 0.0894);

MVP

0.23

MPC

0.020

ClinPred

0.080

GERP RS

1.4

Varity_R

0.26

gMVP

0.36

Mutation Taster

=95/5

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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NM_001242394.2:c.635A>C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over