Genetic Variant ENST00000011473.6:c.19T>G (chr7-106112511-A-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000011473.6(SYPL1):c.19T>G(p.Leu7Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000729 in 1,371,716 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.3e-7 ( 0 hom. )

Consequence

SYPL1
ENST00000011473.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.248

Publications

0 publications found

Variant links:

Genes affected

SYPL1 (HGNC:11507): (synaptophysin like 1) Predicted to be involved in chemical synaptic transmission. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

SYPL1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.051441997).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000011473.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SYPL1	NM_001381910.1	c.19T>G	p.Leu7Val	missense	Exon 1 of 7	NP_001368839.1	A0A994J846
SYPL1	NM_006754.5	c.19T>G	p.Leu7Val	missense	Exon 1 of 6	NP_006745.1	Q16563-1
SYPL1	NM_001381918.1	c.19T>G	p.Leu7Val	missense	Exon 1 of 7	NP_001368847.1	A0A994J5J4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SYPL1	ENST00000011473.6	TSL:1	c.19T>G	p.Leu7Val	missense	Exon 1 of 6	ENSP00000011473.2	Q16563-1
SYPL1	ENST00000706299.1		c.19T>G	p.Leu7Val	missense	Exon 1 of 7	ENSP00000516340.1	A0A994J846
SYPL1	ENST00000706298.1		c.19T>G	p.Leu7Val	missense	Exon 1 of 7	ENSP00000516339.1	A0A994J5J4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000700

AC:

AN:

142772

AF XY:

0.0000126

show subpopulations

Gnomad AFR exome

AF:

0.000179

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.29e-7

AC:

AN:

1371716

Hom.:

Cov.:

AF XY:

0.00000147

AC XY:

AN XY:

678638

show subpopulations

African (AFR)

AF:

0.0000356

AC:

AN:

28056

American (AMR)

AF:

0.00

AC:

AN:

32764

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24194

East Asian (EAS)

AF:

0.00

AC:

AN:

30242

South Asian (SAS)

AF:

0.00

AC:

AN:

75142

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47408

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5516

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1071654

Other (OTH)

AF:

0.00

AC:

AN:

56740

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.53

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.036

Eigen

Benign

-0.99

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.015

LIST_S2

Benign

0.47

M_CAP

Benign

0.022

MetaRNN

Benign

0.051

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.14

PhyloP100

-0.25

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-0.15

REVEL

Benign

0.025

Sift

Benign

0.12

Sift4G

Benign

0.24

Polyphen

0.0030

Vest4

0.28

MutPred

0.22

Loss of helix (P = 0.0167)

MVP

0.12

MPC

0.12

ClinPred

0.025

GERP RS

-1.2

PromoterAI

0.17

Neutral

(source)

Varity_R

0.058

gMVP

0.40

Mutation Taster

=99/1

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over