Genetic Variant SNAPC1:p.Ala13Val (chr14-61762498-C-T) – 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_003082.4(SNAPC1):c.38C>T(p.Ala13Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000496 in 1,410,018 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 29)

Exomes 𝑓: 0.0000038 ( 0 hom. )

Consequence

SNAPC1
NM_003082.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0490

Publications

2 publications found

Variant links:

Genes affected

SNAPC1 (HGNC:11134): (small nuclear RNA activating complex polypeptide 1) Predicted to enable sequence-specific DNA binding activity. Predicted to be involved in snRNA transcription by RNA polymerase II and snRNA transcription by RNA polymerase III. Located in nucleolus and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

SNAPC1 links:

ENSG00000258964 (HGNC:):

ENSG00000258964 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=0.10398543).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003082.4. 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
	SNAPC1	NM_003082.4	MANE Select	c.38C>T	p.Ala13Val	missense	Exon 1 of 10	NP_003073.1	Q16533

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SNAPC1	ENST00000216294.5	TSL:1 MANE Select	c.38C>T	p.Ala13Val	missense	Exon 1 of 10	ENSP00000216294.4	Q16533
SNAPC1	ENST00000923634.1		c.38C>T	p.Ala13Val	missense	Exon 1 of 11	ENSP00000593693.1
SNAPC1	ENST00000923637.1		c.38C>T	p.Ala13Val	missense	Exon 1 of 11	ENSP00000593696.1

Frequencies

GnomAD3 genomes

AF:

0.0000198

AC:

AN:

100880

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000769

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

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:

0.0000125

AC:

AN:

240132

AF XY:

0.0000230

show subpopulations

Gnomad AFR exome

AF:

0.0000661

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000118

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000382

AC:

AN:

1309138

Hom.:

Cov.:

AF XY:

0.00000775

AC XY:

AN XY:

645126

show subpopulations

African (AFR)

AF:

0.0000688

AC:

AN:

29080

American (AMR)

AF:

0.00

AC:

AN:

36450

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21754

East Asian (EAS)

AF:

0.0000639

AC:

AN:

31302

South Asian (SAS)

AF:

0.00

AC:

AN:

63192

European-Finnish (FIN)

AF:

0.00

AC:

AN:

45144

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4914

European-Non Finnish (NFE)

AF:

9.75e-7

AC:

AN:

1025746

Other (OTH)

AF:

0.00

AC:

AN:

51556

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.445

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:

0.0000198

AC:

AN:

100880

Hom.:

Cov.:

AF XY:

0.0000204

AC XY:

AN XY:

48986

show subpopulations

African (AFR)

AF:

0.0000769

AC:

AN:

26004

American (AMR)

AF:

0.00

AC:

AN:

8900

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2306

East Asian (EAS)

AF:

0.00

AC:

AN:

3304

South Asian (SAS)

AF:

0.00

AC:

AN:

2382

European-Finnish (FIN)

AF:

0.00

AC:

AN:

7892

Middle Eastern (MID)

AF:

0.00

AC:

AN:

192

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

47986

Other (OTH)

AF:

0.00

AC:

AN:

1322

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.00000824

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

0.096

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.57

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.014

Eigen

Benign

-0.78

Eigen_PC

Benign

-0.71

FATHMM_MKL

Benign

0.55

LIST_S2

Benign

0.62

M_CAP

Benign

0.0072

MetaRNN

Benign

0.10

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

PhyloP100

0.049

PrimateAI

Benign

0.35

PROVEAN

Benign

-1.1

REVEL

Benign

0.017

Sift

Benign

0.47

Sift4G

Benign

1.0

Polyphen

0.0080

Vest4

0.15

MutPred

0.41

Gain of catalytic residue at L15 (P = 0.0193)

MVP

0.067

MPC

0.046

ClinPred

0.059

GERP RS

1.2

PromoterAI

-0.061

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.080

gMVP

0.38

Mutation Taster

=95/5

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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