rs3812565

chr9-136378050-T-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_003086.4(SNAPC4):c.3777A>G(p.Leu1259=) 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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.79

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]

ACMG classification

Verdict is Benign. Variant got -15 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_single_submitter, 1 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	UniProt
SNAPC4	NM_003086.4	c.3777A>G	p.Leu1259=	synonymous_variant	22/24	ENST00000684778.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SNAPC4	ENST00000684778.1	c.3777A>G	p.Leu1259=	synonymous_variant	22/24		NM_003086.4	P1
SNAPC4	ENST00000298532.2	c.3777A>G	p.Leu1259=	synonymous_variant	21/23	1		P1
SNAPC4	ENST00000637388.2	c.3777A>G	p.Leu1259=	synonymous_variant	22/24	5		P1
SNAPC4	ENST00000689006.1	c.*2990A>G		3_prime_UTR_variant, NMD_transcript_variant	22/24

Frequencies

GnomAD3 genomes AF: 0.360 AC: 54503 AN: 151404 Hom.: 10057 Cov.: 33

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

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.: 46 AF XY: 0.376 AC XY: 265730 AN XY: 706510

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.: 33 AF XY: 0.358 AC XY: 26489 AN XY: 74026

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:1

Revision: criteria provided, single submitter

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 -

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

Other links and lift over

dbSNP: rs3812565; hg19: chr9-139272502; COSMIC: COSV53731140; COSMIC: COSV53731140;