Genetic Variant NM_003086.4:c.2487T>G (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

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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