Genetic Variant SNAPC4:p.Ser1407Ser (chr9-136377606-A-G) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_003086.4(SNAPC4):c.4221T>C(p.Ser1407Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.41 in 1,543,320 control chromosomes in the GnomAD database, including 132,097 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.38 ( 11391 hom., cov: 34)

Exomes 𝑓: 0.41 ( 120706 hom. )

Consequence

SNAPC4
NM_003086.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.265

Publications

47 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 9-136377606-A-G is Benign according to our data. Variant chr9-136377606-A-G is described in ClinVar as Benign. ClinVar VariationId is 402489.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.265 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.464 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003086.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SNAPC4	NM_003086.4	MANE Select	c.4221T>C	p.Ser1407Ser	synonymous	Exon 22 of 24	NP_003077.2
SNAPC4	NM_001394201.1		c.4221T>C	p.Ser1407Ser	synonymous	Exon 22 of 24	NP_001381130.1
SNAPC4	NM_001394202.1		c.4137T>C	p.Ser1379Ser	synonymous	Exon 22 of 24	NP_001381131.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SNAPC4	ENST00000684778.1	MANE Select	c.4221T>C	p.Ser1407Ser	synonymous	Exon 22 of 24	ENSP00000510559.1
SNAPC4	ENST00000298532.2	TSL:1	c.4221T>C	p.Ser1407Ser	synonymous	Exon 21 of 23	ENSP00000298532.2
SNAPC4	ENST00000637388.2	TSL:5	c.4221T>C	p.Ser1407Ser	synonymous	Exon 22 of 24	ENSP00000490037.2

Frequencies

GnomAD3 genomes

AF:

0.380

AC:

57786

AN:

151968

Hom.:

11373

Cov.:

show subpopulations

Gnomad AFR

AF:

0.293

Gnomad AMI

AF:

0.414

Gnomad AMR

AF:

0.472

Gnomad ASJ

AF:

0.355

Gnomad EAS

AF:

0.311

Gnomad SAS

AF:

0.330

Gnomad FIN

AF:

0.414

Gnomad MID

AF:

0.199

Gnomad NFE

AF:

0.419

Gnomad OTH

AF:

0.354

GnomAD2 exomes

AF:

0.404

AC:

82573

AN:

204442

AF XY:

0.398

show subpopulations

Gnomad AFR exome

AF:

0.289

Gnomad AMR exome

AF:

0.537

Gnomad ASJ exome

AF:

0.356

Gnomad EAS exome

AF:

0.298

Gnomad FIN exome

AF:

0.414

Gnomad NFE exome

AF:

0.423

Gnomad OTH exome

AF:

0.413

GnomAD4 exome

AF:

0.413

AC:

574608

AN:

1391234

Hom.:

120706

Cov.:

AF XY:

0.410

AC XY:

280112

AN XY:

683956

show subpopulations

African (AFR)

AF:

0.284

AC:

8864

AN:

31228

American (AMR)

AF:

0.536

AC:

18714

AN:

34894

Ashkenazi Jewish (ASJ)

AF:

0.352

AC:

7711

AN:

21884

East Asian (EAS)

AF:

0.318

AC:

12341

AN:

38814

South Asian (SAS)

AF:

0.321

AC:

24929

AN:

77760

European-Finnish (FIN)

AF:

0.416

AC:

20703

AN:

49708

Middle Eastern (MID)

AF:

0.241

AC:

1306

AN:

5430

European-Non Finnish (NFE)

AF:

0.426

AC:

457525

AN:

1074364

Other (OTH)

AF:

0.394

AC:

22515

AN:

57152

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

19504

39008

58511

78015

97519

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14326

28652

42978

57304

71630

<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:

0.380

AC:

57855

AN:

152086

Hom.:

11391

Cov.:

AF XY:

0.379

AC XY:

28172

AN XY:

74346

show subpopulations

African (AFR)

AF:

0.294

AC:

12178

AN:

41484

American (AMR)

AF:

0.473

AC:

7234

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.355

AC:

1231

AN:

3464

East Asian (EAS)

AF:

0.310

AC:

1592

AN:

5140

South Asian (SAS)

AF:

0.330

AC:

1593

AN:

4828

European-Finnish (FIN)

AF:

0.414

AC:

4386

AN:

10594

Middle Eastern (MID)

AF:

0.214

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.419

AC:

28449

AN:

67972

Other (OTH)

AF:

0.356

AC:

752

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1927

3854

5782

7709

9636

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

548

1096

1644

2192

2740

<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:

0.409

Hom.:

11809

Bravo

AF:

0.378

Asia WGS

AF:

0.387

AC:

1346

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: MAF

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.30

(source)

DANN

Benign

0.33

PhyloP100

-0.27

Mutation Taster

=100/0

polymorphism (auto)

(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

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over