9-15422946-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001039697.2(SNAPC3):c.67G>A(p.Gly23Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000189 in 1,531,862 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

SNAPC3
NM_001039697.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.671

Variant links:

Genes affected

SNAPC3 (HGNC:11136): (small nuclear RNA activating complex polypeptide 3) Predicted to enable RNA polymerase III type 3 promoter sequence-specific DNA binding activity and bent DNA binding activity. Predicted to contribute to RNA polymerase II cis-regulatory region sequence-specific DNA binding activity and core promoter sequence-specific DNA binding activity. Predicted to be involved in snRNA transcription by RNA polymerase II and snRNA transcription by RNA polymerase III. Located in nuclear body and nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

SNAPC3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.00609982).

BP6

Variant 9-15422946-G-A is Benign according to our data. Variant chr9-15422946-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2468645.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SNAPC3	NM_001039697.2 linkuse as main transcript	c.67G>A	p.Gly23Ser	missense_variant	1/9	ENST00000380821.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SNAPC3	ENST00000380821.8 linkuse as main transcript	c.67G>A	p.Gly23Ser	missense_variant	1/9	1	NM_001039697.2	P1

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152262

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000961

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000512

AC:

AN:

136628

Hom.:

AF XY:

0.0000542

AC XY:

AN XY:

73802

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000791

Gnomad SAS 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:

0.0000159

AC:

AN:

1379600

Hom.:

Cov.:

AF XY:

0.0000205

AC XY:

AN XY:

681994

show subpopulations

Gnomad4 AFR exome

AF:

0.0000341

Gnomad4 AMR exome

AF:

0.0000378

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000228

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000651

Gnomad4 OTH exome

AF:

0.0000876

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152262

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74396

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000961

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000491

ExAC

AF:

0.0000360

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 27, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.65

Cadd

Benign

0.33

Dann

Benign

0.83

DEOGEN2

Benign

0.0037

T;T;.

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.011

M_CAP

Benign

0.0023

MetaRNN

Benign

0.0061

T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-0.49

N;N;.

MutationTaster

Benign

1.0

PrimateAI

Benign

0.35

PROVEAN

Benign

0.55

N;.;N

REVEL

Benign

0.023

Sift

Benign

1.0

T;.;T

Sift4G

Benign

1.0

T;T;T

Polyphen

0.0010

B;B;.

Vest4

0.16

MutPred

0.11

Loss of glycosylation at S22 (P = 0.0323);Loss of glycosylation at S22 (P = 0.0323);Loss of glycosylation at S22 (P = 0.0323);

MVP

0.16

MPC

0.023

ClinPred

0.031

GERP RS

-1.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.030

gMVP

0.25

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