Variant rs3812565 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_003086.4(SNAPC4):c.3777A>G(p.Leu1259Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.379 in 1,576,956 control chromosomes in the GnomAD database, including 115,843 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.36 ( 10086 hom., cov: 33)

Exomes 𝑓: 0.38 ( 105757 hom. )

Consequence

SNAPC4
NM_003086.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.79

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 9-136378050-T-C is Benign according to our data. Variant chr9-136378050-T-C is described in ClinVar as [Benign]. Clinvar id is 402490.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.79 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.457 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SNAPC4	NM_003086.4 linkuse as main transcript	c.3777A>G	p.Leu1259Leu	synonymous_variant	22/24	ENST00000684778.1	NP_003077.2	Q5SXM2A0A024R8F4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SNAPC4	ENST00000684778.1 linkuse as main transcript	c.3777A>G	p.Leu1259Leu	synonymous_variant	22/24		NM_003086.4	ENSP00000510559.1		Q5SXM2

Frequencies

GnomAD3 genomes

AF:

0.360

AC:

54503

AN:

151404

Hom.:

10057

Cov.:

show subpopulations

Gnomad AFR

AF:

0.311

Gnomad AMI

AF:

0.375

Gnomad AMR

AF:

0.465

Gnomad ASJ

AF:

0.327

Gnomad EAS

AF:

0.199

Gnomad SAS

AF:

0.278

Gnomad FIN

AF:

0.368

Gnomad MID

AF:

0.204

Gnomad NFE

AF:

0.386

Gnomad OTH

AF:

0.337

GnomAD3 exomes

AF:

0.372

AC:

68165

AN:

183368

Hom.:

13457

AF XY:

0.360

AC XY:

36634

AN XY:

101660

show subpopulations

Gnomad AFR exome

AF:

0.310

Gnomad AMR exome

AF:

0.527

Gnomad ASJ exome

AF:

0.321

Gnomad EAS exome

AF:

0.184

Gnomad SAS exome

AF:

0.283

Gnomad FIN exome

AF:

0.372

Gnomad NFE exome

AF:

0.393

Gnomad OTH exome

AF:

0.374

GnomAD4 exome

AF:

0.380

AC:

542361

AN:

1425434

Hom.:

105757

Cov.:

AF XY:

0.376

AC XY:

265730

AN XY:

706510

show subpopulations

Gnomad4 AFR exome

AF:

0.303

Gnomad4 AMR exome

AF:

0.523

Gnomad4 ASJ exome

AF:

0.322

Gnomad4 EAS exome

AF:

0.220

Gnomad4 SAS exome

AF:

0.279

Gnomad4 FIN exome

AF:

0.369

Gnomad4 NFE exome

AF:

0.395

Gnomad4 OTH exome

AF:

0.360

GnomAD4 genome

AF:

0.360

AC:

54584

AN:

151522

Hom.:

10086

Cov.:

AF XY:

0.358

AC XY:

26489

AN XY:

74026

show subpopulations

Gnomad4 AFR

AF:

0.312

Gnomad4 AMR

AF:

0.466

Gnomad4 ASJ

AF:

0.327

Gnomad4 EAS

AF:

0.198

Gnomad4 SAS

AF:

0.279

Gnomad4 FIN

AF:

0.368

Gnomad4 NFE

AF:

0.386

Gnomad4 OTH

AF:

0.338

Alfa

AF:

0.379

Hom.:

3646

Bravo

AF:

0.363

Asia WGS

AF:

0.288

AC:

1001

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

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

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

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.40

DANN

Benign

0.74

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over