Genetic Variant SNAPC2:p.Pro45Ser (chr19-7920499-C-T) – 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_003083.4(SNAPC2):c.133C>T(p.Pro45Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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. P45T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SNAPC2
NM_003083.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.73

Publications

0 publications found

Variant links:

Genes affected

SNAPC2 (HGNC:11135): (small nuclear RNA activating complex polypeptide 2) This gene encodes a subunit of the snRNA-activating protein complex which is associated with the TATA box-binding protein. The encoded protein is necessary for RNA polymerase II and III dependent small-nuclear RNA gene transcription. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2009]

SNAPC2 links:

ENSG00000260500 (HGNC:):

ENSG00000260500 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=0.33482707).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003083.4. 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
	SNAPC2	NM_003083.4	MANE Select	c.133C>T	p.Pro45Ser	missense	Exon 1 of 5	NP_003074.1	Q13487

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SNAPC2	ENST00000221573.11	TSL:1 MANE Select	c.133C>T	p.Pro45Ser	missense	Exon 1 of 5	ENSP00000221573.5	Q13487
SNAPC2	ENST00000853925.1		c.133C>T	p.Pro45Ser	missense	Exon 1 of 5	ENSP00000523984.1
SNAPC2	ENST00000971261.1		c.133C>T	p.Pro45Ser	missense	Exon 1 of 4	ENSP00000641320.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1345578

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

663042

African (AFR)

AF:

0.00

AC:

AN:

27152

American (AMR)

AF:

0.00

AC:

AN:

31106

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23278

East Asian (EAS)

AF:

0.00

AC:

AN:

31606

South Asian (SAS)

AF:

0.00

AC:

AN:

75326

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33322

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4180

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1063532

Other (OTH)

AF:

0.00

AC:

AN:

56076

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.49

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.40

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.060

Eigen

Uncertain

0.30

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Benign

0.67

LIST_S2

Benign

0.78

M_CAP

Pathogenic

0.60

MetaRNN

Benign

0.33

MetaSVM

Benign

-0.73

MutationAssessor

Benign

2.0

PhyloP100

1.7

PrimateAI

Uncertain

0.69

PROVEAN

Pathogenic

-4.5

REVEL

Benign

0.082

Sift

Benign

0.24

Sift4G

Benign

0.089

Polyphen

0.96

Vest4

0.40

MutPred

0.20

Gain of helix (P = 0.027)

MVP

0.61

MPC

0.32

ClinPred

0.99

GERP RS

4.1

PromoterAI

0.021

Neutral

(source)

Varity_R

0.21

gMVP

0.33

Mutation Taster

=96/4

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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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