Variant 9-15459753-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001039697.2(SNAPC3):c.1123G>A(p.Asp375Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000089 in 1,461,198 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 0.0000089 ( 0 hom. )

Consequence

SNAPC3
NM_001039697.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.70

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.30545712).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SNAPC3	NM_001039697.2 linkuse as main transcript	c.1123G>A	p.Asp375Asn	missense_variant	9/9	ENST00000380821.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
SNAPC3	ENST00000380821.8 linkuse as main transcript	c.1123G>A	p.Asp375Asn	missense_variant	9/9	1	NM_001039697.2	P1
SNAPC3	ENST00000610884.4 linkuse as main transcript	c.1123G>A	p.Asp375Asn	missense_variant	9/12	1		P1
SNAPC3	ENST00000467062.5 linkuse as main transcript	c.1123G>A	p.Asp375Asn	missense_variant, NMD_transcript_variant	9/12	1
SNAPC3	ENST00000490969.5 linkuse as main transcript	c.1123G>A	p.Asp375Asn	missense_variant, NMD_transcript_variant	9/10	1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000120

AC:

AN:

250698

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135512

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.00000890

AC:

AN:

1461198

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

726902

show subpopulations

Gnomad4 AFR exome

AF:

0.000209

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000113

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 05, 2022

The c.1123G>A (p.D375N) alteration is located in exon 9 (coding exon 9) of the SNAPC3 gene. This alteration results from a G to A substitution at nucleotide position 1123, causing the aspartic acid (D) at amino acid position 375 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.48

Cadd

Pathogenic

Dann

Uncertain

1.0

DEOGEN2

Benign

0.027

T;T

Eigen

Uncertain

0.68

Eigen_PC

Pathogenic

0.72

FATHMM_MKL

Uncertain

0.95

M_CAP

Benign

0.015

MetaRNN

Benign

0.31

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.8

L;L

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-2.0

N;.

REVEL

Benign

0.17

Sift

Benign

0.20

T;.

Sift4G

Benign

0.13

T;T

Polyphen

0.95

P;P

Vest4

0.28

MutPred

0.51

Gain of catalytic residue at D375 (P = 0.0261);Gain of catalytic residue at D375 (P = 0.0261);

MVP

0.62

MPC

0.17

ClinPred

0.65

GERP RS

5.9

Varity_R

0.20

gMVP

0.59

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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