Genetic Variant NM_003825.4:c.575A>G (chr15-42531417-A-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_003825.4(SNAP23):c.575A>G(p.Asp192Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SNAP23
NM_003825.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.55

Publications

0 publications found

Variant links:

Genes affected

SNAP23 (HGNC:11131): (synaptosome associated protein 23) Specificity of vesicular transport is regulated, in part, by the interaction of a vesicle-associated membrane protein termed synaptobrevin/VAMP with a target compartment membrane protein termed syntaxin. These proteins, together with SNAP25 (synaptosome-associated protein of 25 kDa), form a complex which serves as a binding site for the general membrane fusion machinery. Synaptobrevin/VAMP and syntaxin are believed to be involved in vesicular transport in most, if not all cells, while SNAP25 is present almost exclusively in the brain, suggesting that a ubiquitously expressed homolog of SNAP25 exists to facilitate transport vesicle/target membrane fusion in other tissues. The protein encoded by this gene is structurally and functionally similar to SNAP25 and binds tightly to multiple syntaxins and synaptobrevins/VAMPs. It is an essential component of the high affinity receptor for the general membrane fusion machinery and is an important regulator of transport vesicle docking and fusion. Two alternative transcript variants encoding different protein isoforms have been described for this gene. [provided by RefSeq, Jul 2008]

SNAP23 links:

ENSG00000285942 (HGNC:):

ENSG00000285942 links:

LRRC57 (HGNC:26719): (leucine rich repeat containing 57) Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

LRRC57 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.34395677).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003825.4. 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
	SNAP23	NM_003825.4	MANE Select	c.575A>G	p.Asp192Gly	missense	Exon 8 of 8	NP_003816.2
	SNAP23	NM_130798.3		c.416A>G	p.Asp139Gly	missense	Exon 7 of 7	NP_570710.1	O00161-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SNAP23	ENST00000249647.8	TSL:1 MANE Select	c.575A>G	p.Asp192Gly	missense	Exon 8 of 8	ENSP00000249647.3	O00161-1
SNAP23	ENST00000397138.5	TSL:1	c.416A>G	p.Asp139Gly	missense	Exon 6 of 6	ENSP00000380327.1	O00161-2
ENSG00000285942	ENST00000650210.1		n.679-348T>C		intron	N/A	ENSP00000497618.1	A0A3B3ISV5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1398844

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

693716

African (AFR)

AF:

0.00

AC:

AN:

30748

American (AMR)

AF:

0.00

AC:

AN:

35836

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24724

East Asian (EAS)

AF:

0.00

AC:

AN:

36786

South Asian (SAS)

AF:

0.00

AC:

AN:

73062

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51140

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4464

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1084318

Other (OTH)

AF:

0.00

AC:

AN:

57766

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

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

0.10

BayesDel_addAF

Pathogenic

0.21

BayesDel_noAF

Uncertain

0.060

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.58

Eigen

Uncertain

0.49

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.93

M_CAP

Benign

0.025

MetaRNN

Benign

0.34

MetaSVM

Uncertain

-0.28

MutationAssessor

Uncertain

2.3

PhyloP100

8.6

PrimateAI

Benign

0.46

PROVEAN

Uncertain

-2.7

REVEL

Benign

0.20

Sift

Benign

0.077

Sift4G

Benign

0.092

Polyphen

0.78

Vest4

0.49

MutPred

0.51

Gain of MoRF binding (P = 0.0306)

MVP

0.32

MPC

1.0

ClinPred

0.96

GERP RS

5.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.26

gMVP

0.90

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over