Genetic Variant SNAPC2:p.Pro45Ala (chr19-7920499-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003083.4(SNAPC2):c.133C>G(p.Pro45Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000132 in 151,720 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 𝑓 0.000013 ( 0 hom., cov: 31)

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.19422719).

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>G	p.Pro45Ala	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>G	p.Pro45Ala	missense	Exon 1 of 5	ENSP00000221573.5	Q13487
SNAPC2	ENST00000853925.1		c.133C>G	p.Pro45Ala	missense	Exon 1 of 5	ENSP00000523984.1
SNAPC2	ENST00000971261.1		c.133C>G	p.Pro45Ala	missense	Exon 1 of 4	ENSP00000641320.1

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151610

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000390

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.0000132

AC:

AN:

151720

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74124

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41338

American (AMR)

AF:

0.00

AC:

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.000391

AC:

AN:

5116

South Asian (SAS)

AF:

0.00

AC:

AN:

4780

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10574

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67866

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.43

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.034

Eigen

Benign

0.0075

Eigen_PC

Benign

0.054

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.76

M_CAP

Pathogenic

0.42

MetaRNN

Benign

0.19

MetaSVM

Benign

-0.95

MutationAssessor

Benign

2.0

PhyloP100

1.7

PrimateAI

Uncertain

0.69

PROVEAN

Uncertain

-4.3

REVEL

Benign

0.064

Sift

Benign

0.49

Sift4G

Benign

0.44

Polyphen

0.62

Vest4

0.29

MutPred

0.17

Loss of loop (P = 0.0128)

MVP

0.54

MPC

0.27

ClinPred

0.99

GERP RS

4.1

PromoterAI

-0.017

Neutral

(source)

Varity_R

0.16

gMVP

0.19

Mutation Taster

=97/3

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over