Genetic Variant SNAPC4:p.Val829Val (chr9-136380752-A-C) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_003086.4(SNAPC4):c.2487T>G(p.Val829Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.431 in 1,581,976 control chromosomes in the GnomAD database, including 149,854 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.43 ( 13898 hom., cov: 33)

Exomes 𝑓: 0.43 ( 135956 hom. )

Consequence

SNAPC4
NM_003086.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.41

Publications

54 publications found

Variant links:

Genes affected

SNAPC4 (HGNC:11137): (small nuclear RNA activating complex polypeptide 4) This gene encodes the largest subunit of the small nuclear RNA-activating protein (SNAP) complex. The encoded protein contains a Myb DNA-binding domain, and is essential for RNA polymerase II and III polymerase transcription from small nuclear RNA promoters. A mutation in this gene is associated with ankylosing spondylitis. [provided by RefSeq, Jul 2016]

SNAPC4 Gene-Disease associations (from GenCC):

neurodevelopmental disorder with motor regression, progressive spastic paraplegia, and oromotor dysfunction
Inheritance: AR Classification: MODERATE Submitted by: Baylor College of Medicine Research Center, G2P

SNAPC4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.06).

BP7

Synonymous conserved (PhyloP=-2.41 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.51 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SNAPC4	NM_003086.4 link	c.2487T>G	p.Val829Val	synonymous_variant	Exon 20 of 24	ENST00000684778.1	NP_003077.2	Q5SXM2A0A024R8F4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SNAPC4	ENST00000684778.1 link	c.2487T>G	p.Val829Val	synonymous_variant	Exon 20 of 24		NM_003086.4	ENSP00000510559.1		Q5SXM2

Frequencies

GnomAD3 genomes

AF:

0.425

AC:

64584

AN:

151896

Hom.:

13868

Cov.:

show subpopulations

Gnomad AFR

AF:

0.394

Gnomad AMI

AF:

0.443

Gnomad AMR

AF:

0.519

Gnomad ASJ

AF:

0.451

Gnomad EAS

AF:

0.312

Gnomad SAS

AF:

0.336

Gnomad FIN

AF:

0.416

Gnomad MID

AF:

0.310

Gnomad NFE

AF:

0.439

Gnomad OTH

AF:

0.423

GnomAD2 exomes

AF:

0.430

AC:

106287

AN:

246940

AF XY:

0.421

show subpopulations

Gnomad AFR exome

AF:

0.389

Gnomad AMR exome

AF:

0.565

Gnomad ASJ exome

AF:

0.452

Gnomad EAS exome

AF:

0.297

Gnomad FIN exome

AF:

0.420

Gnomad NFE exome

AF:

0.443

Gnomad OTH exome

AF:

0.448

GnomAD4 exome

AF:

0.432

AC:

617285

AN:

1429962

Hom.:

135956

Cov.:

AF XY:

0.428

AC XY:

304985

AN XY:

712972

show subpopulations

African (AFR)

AF:

0.384

AC:

12659

AN:

32948

American (AMR)

AF:

0.565

AC:

25116

AN:

44432

Ashkenazi Jewish (ASJ)

AF:

0.447

AC:

11556

AN:

25852

East Asian (EAS)

AF:

0.317

AC:

12539

AN:

39502

South Asian (SAS)

AF:

0.327

AC:

27976

AN:

85636

European-Finnish (FIN)

AF:

0.421

AC:

21976

AN:

52144

Middle Eastern (MID)

AF:

0.340

AC:

1940

AN:

5706

European-Non Finnish (NFE)

AF:

0.441

AC:

478353

AN:

1084404

Other (OTH)

AF:

0.424

AC:

25170

AN:

59338

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.454

Heterozygous variant carriers

14059

28118

42177

56236

70295

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14238

28476

42714

56952

71190

<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:

0.425

AC:

64674

AN:

152014

Hom.:

13898

Cov.:

AF XY:

0.423

AC XY:

31426

AN XY:

74284

show subpopulations

African (AFR)

AF:

0.394

AC:

16342

AN:

41474

American (AMR)

AF:

0.520

AC:

7939

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.451

AC:

1564

AN:

3470

East Asian (EAS)

AF:

0.311

AC:

1606

AN:

5164

South Asian (SAS)

AF:

0.336

AC:

1618

AN:

4814

European-Finnish (FIN)

AF:

0.416

AC:

4396

AN:

10568

Middle Eastern (MID)

AF:

0.327

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.439

AC:

29812

AN:

67932

Other (OTH)

AF:

0.425

AC:

898

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1953

3906

5858

7811

9764

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

592

1184

1776

2368

2960

<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:

0.439

Hom.:

23567

Bravo

AF:

0.431

Asia WGS

AF:

0.400

AC:

1392

AN:

3478

EpiCase

AF:

0.416

EpiControl

AF:

0.433

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.1

CADD

Benign

0.16

(source)

DANN

Benign

0.51

PhyloP100

-2.4

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over