Genetic Variant NM_003083.4:c.170G>C (chr19-7920536-G-C) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_003083.4(SNAPC2):c.170G>C(p.Arg57Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000272 in 1,425,382 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R57G) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00017 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00028 ( 0 hom. )

Consequence

SNAPC2
NM_003083.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.929

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.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.765

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.170G>C	p.Arg57Pro	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.170G>C	p.Arg57Pro	missense	Exon 1 of 5	ENSP00000221573.5	Q13487
SNAPC2	ENST00000853925.1		c.170G>C	p.Arg57Pro	missense	Exon 1 of 5	ENSP00000523984.1
SNAPC2	ENST00000971261.1		c.170G>C	p.Arg57Pro	missense	Exon 1 of 4	ENSP00000641320.1

Frequencies

GnomAD3 genomes

AF:

0.000172

AC:

AN:

151424

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000486

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000947

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000295

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000175

AC:

AN:

40030

AF XY:

0.000170

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000457

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000202

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000284

AC:

362

AN:

1273958

Hom.:

Cov.:

AF XY:

0.000277

AC XY:

173

AN XY:

623812

show subpopulations

African (AFR)

AF:

0.0000402

AC:

AN:

24872

American (AMR)

AF:

0.000401

AC:

AN:

19938

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19844

East Asian (EAS)

AF:

0.00

AC:

AN:

29204

South Asian (SAS)

AF:

0.0000304

AC:

AN:

65744

European-Finnish (FIN)

AF:

0.0000967

AC:

AN:

31026

Middle Eastern (MID)

AF:

0.000267

AC:

AN:

3742

European-Non Finnish (NFE)

AF:

0.000319

AC:

328

AN:

1026758

Other (OTH)

AF:

0.000360

AC:

AN:

52830

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

107

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<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:

0.000172

AC:

AN:

151424

Hom.:

Cov.:

AF XY:

0.000189

AC XY:

AN XY:

73920

show subpopulations

African (AFR)

AF:

0.0000486

AC:

AN:

41144

American (AMR)

AF:

0.000197

AC:

AN:

15218

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5144

South Asian (SAS)

AF:

0.00

AC:

AN:

4764

European-Finnish (FIN)

AF:

0.0000947

AC:

AN:

10562

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.000295

AC:

AN:

67818

Other (OTH)

AF:

0.00

AC:

AN:

2082

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.542

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:

0.000154

Hom.:

Bravo

AF:

0.000242

ExAC

AF:

0.000102

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

Pathogenic

0.89

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Uncertain

-0.080

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.095

Eigen

Uncertain

0.25

Eigen_PC

Benign

0.15

FATHMM_MKL

Benign

0.67

LIST_S2

Benign

0.79

M_CAP

Pathogenic

0.87

MetaRNN

Pathogenic

0.76

MetaSVM

Benign

-0.46

MutationAssessor

Uncertain

2.0

PhyloP100

0.93

PrimateAI

Uncertain

0.69

PROVEAN

Pathogenic

-5.7

REVEL

Benign

0.28

Sift

Uncertain

0.0080

Sift4G

Benign

0.089

Polyphen

0.98

Vest4

0.60

MVP

0.80

MPC

0.41

ClinPred

0.59

GERP RS

4.1

PromoterAI

0.051

Neutral

(source)

Varity_R

0.75

gMVP

0.78

Mutation Taster

=65/35

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