Variant chr9-136377606-A-G 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.4221T>C(p.Ser1407=) 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

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=-0.92).

BP6

Variant 9-136377606-A-G is Benign according to our data. Variant chr9-136377606-A-G is described in ClinVar as [Benign]. Clinvar id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SNAPC4	NM_003086.4 linkuse as main transcript	c.4221T>C	p.Ser1407=	synonymous_variant	22/24	ENST00000684778.1	NP_003077.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
SNAPC4	ENST00000684778.1 linkuse as main transcript	c.4221T>C	p.Ser1407=	synonymous_variant	22/24		NM_003086.4	ENSP00000510559	P1
SNAPC4	ENST00000298532.2 linkuse as main transcript	c.4221T>C	p.Ser1407=	synonymous_variant	21/23	1		ENSP00000298532	P1
SNAPC4	ENST00000637388.2 linkuse as main transcript	c.4221T>C	p.Ser1407=	synonymous_variant	22/24	5		ENSP00000490037	P1
SNAPC4	ENST00000689006.1 linkuse as main transcript	c.*3434T>C		3_prime_UTR_variant, NMD_transcript_variant	22/24			ENSP00000509362

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

GnomAD3 exomes

AF:

0.404

AC:

82573

AN:

204442

Hom.:

17316

AF XY:

0.398

AC XY:

43903

AN XY:

110382

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 SAS exome

AF:

0.329

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

Gnomad4 AFR exome

AF:

0.284

Gnomad4 AMR exome

AF:

0.536

Gnomad4 ASJ exome

AF:

0.352

Gnomad4 EAS exome

AF:

0.318

Gnomad4 SAS exome

AF:

0.321

Gnomad4 FIN exome

AF:

0.416

Gnomad4 NFE exome

AF:

0.426

Gnomad4 OTH exome

AF:

0.394

GnomAD4 genome

AF:

0.380

AC:

57855

AN:

152086

Hom.:

11391

Cov.:

AF XY:

0.379

AC XY:

28172

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.294

Gnomad4 AMR

AF:

0.473

Gnomad4 ASJ

AF:

0.355

Gnomad4 EAS

AF:

0.310

Gnomad4 SAS

AF:

0.330

Gnomad4 FIN

AF:

0.414

Gnomad4 NFE

AF:

0.419

Gnomad4 OTH

AF:

0.356

Alfa

AF:

0.411

Hom.:

9758

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

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

-0.92

CADD

Benign

0.30

DANN

Benign

0.33

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