Genetic Variant NM_003083.4:c.49G>A (chr19-7920415-G-A) – 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.49G>A(p.Glu17Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000007 in 1,429,332 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

SNAPC2
NM_003083.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.769

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=0.2988504).

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.49G>A	p.Glu17Lys	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.49G>A	p.Glu17Lys	missense	Exon 1 of 5	ENSP00000221573.5	Q13487
SNAPC2	ENST00000853925.1		c.49G>A	p.Glu17Lys	missense	Exon 1 of 5	ENSP00000523984.1
SNAPC2	ENST00000971261.1		c.49G>A	p.Glu17Lys	missense	Exon 1 of 4	ENSP00000641320.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.00e-7

AC:

AN:

1429332

Hom.:

Cov.:

AF XY:

0.00000141

AC XY:

AN XY:

710826

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30716

American (AMR)

AF:

0.00

AC:

AN:

43284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25266

East Asian (EAS)

AF:

0.00

AC:

AN:

37256

South Asian (SAS)

AF:

0.00

AC:

AN:

84338

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39644

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5606

European-Non Finnish (NFE)

AF:

9.06e-7

AC:

AN:

1103876

Other (OTH)

AF:

0.00

AC:

AN:

59346

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

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

Cov.:

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

0.13

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.41

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0045

Eigen

Benign

-0.11

Eigen_PC

Benign

-0.29

FATHMM_MKL

Benign

0.24

LIST_S2

Benign

0.84

M_CAP

Uncertain

0.13

MetaRNN

Benign

0.30

MetaSVM

Benign

-0.90

MutationAssessor

Benign

1.9

PhyloP100

0.77

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

-1.8

REVEL

Benign

0.097

Sift

Benign

0.037

Sift4G

Benign

0.33

Polyphen

0.99

Vest4

0.46

MutPred

0.26

Gain of methylation at E17 (P = 0.0153)

MVP

0.68

MPC

0.33

ClinPred

0.80

GERP RS

1.8

PromoterAI

-0.0037

Neutral

(source)

Varity_R

0.16

gMVP

0.20

Mutation Taster

=100/0

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over