Genetic Variant SNAPC2:p.Pro45Thr (chr19-7920499-C-A) – 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>A(p.Pro45Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000267 in 1,497,190 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: 𝑓 0.0000066 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000022 ( 0 hom. )

Consequence

SNAPC2
NM_003083.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

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:

Genome browser will be placed here

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=0.26009738).

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>A	p.Pro45Thr	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>A	p.Pro45Thr	missense	Exon 1 of 5	ENSP00000221573.5	Q13487
SNAPC2	ENST00000853925.1		c.133C>A	p.Pro45Thr	missense	Exon 1 of 5	ENSP00000523984.1
SNAPC2	ENST00000971261.1		c.133C>A	p.Pro45Thr	missense	Exon 1 of 4	ENSP00000641320.1

Frequencies

GnomAD3 genomes

AF:

0.00000660

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:

0.000195

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

GnomAD2 exomes

AF:

0.0000109

AC:

AN:

91658

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000185

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000223

AC:

AN:

1345580

Hom.:

Cov.:

AF XY:

0.00000151

AC XY:

AN XY:

663044

show subpopulations

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:

0.0000949

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:

1063534

Other (OTH)

AF:

0.00

AC:

AN:

56076

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.00000660

AC:

AN:

151610

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74004

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41218

American (AMR)

AF:

0.00

AC:

AN:

15242

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.000195

AC:

AN:

5132

South Asian (SAS)

AF:

0.00

AC:

AN:

4784

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10574

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67876

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

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:

0.0000113

ExAC

AF:

0.0000380

AC:

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

0.23

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.38

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.060

Eigen

Uncertain

0.27

Eigen_PC

Uncertain

0.25

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.77

M_CAP

Pathogenic

0.57

MetaRNN

Benign

0.26

MetaSVM

Benign

-0.70

MutationAssessor

Benign

2.0

PhyloP100

1.7

PrimateAI

Uncertain

0.71

PROVEAN

Pathogenic

-4.5

REVEL

Benign

0.091

Sift

Benign

0.13

Sift4G

Benign

0.20

Polyphen

0.92

Vest4

0.33

MutPred

0.18

Gain of phosphorylation at P45 (P = 0.0472)

MVP

0.59

MPC

0.32

ClinPred

0.95

GERP RS

4.1

PromoterAI

0.043

Neutral

(source)

Varity_R

0.30

gMVP

0.29

Mutation Taster

=93/7

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over