rs3812570

Positions:

• chr9-136380752-A-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_003086.4(SNAPC4):​c.2487T>G​(p.Val829=) 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.41

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 -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/exons	MANE	UniProt
SNAPC4	NM_003086.4	c.2487T>G	p.Val829=	synonymous_variant	20/24	ENST00000684778.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SNAPC4	ENST00000684778.1	c.2487T>G	p.Val829=	synonymous_variant	20/24		NM_003086.4	P1
SNAPC4	ENST00000298532.2	c.2487T>G	p.Val829=	synonymous_variant	19/23	1		P1
SNAPC4	ENST00000637388.2	c.2487T>G	p.Val829=	synonymous_variant	20/24	5		P1
SNAPC4	ENST00000689006.1	c.*1700T>G		3_prime_UTR_variant, NMD_transcript_variant	20/24

Frequencies

GnomAD3 genomes AF: 0.425 AC: 64584 AN: 151896 Hom.: 13868 Cov.: 33

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

GnomAD3 exomes AF: 0.430 AC: 106287 AN: 246940 Hom.: 23634 AF XY: 0.421 AC XY: 56460 AN XY: 134180

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 SAS exome AF: 0.334

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.: 27 AF XY: 0.428 AC XY: 304985 AN XY: 712972

Gnomad4 AFR exome AF: 0.384

Gnomad4 AMR exome AF: 0.565

Gnomad4 ASJ exome AF: 0.447

Gnomad4 EAS exome AF: 0.317

Gnomad4 SAS exome AF: 0.327

Gnomad4 FIN exome AF: 0.421

Gnomad4 NFE exome AF: 0.441

Gnomad4 OTH exome AF: 0.424

GnomAD4 genome AF: 0.425 AC: 64674 AN: 152014 Hom.: 13898 Cov.: 33 AF XY: 0.423 AC XY: 31426 AN XY: 74284

Gnomad4 AFR AF: 0.394

Gnomad4 AMR AF: 0.520

Gnomad4 ASJ AF: 0.451

Gnomad4 EAS AF: 0.311

Gnomad4 SAS AF: 0.336

Gnomad4 FIN AF: 0.416

Gnomad4 NFE AF: 0.439

Gnomad4 OTH AF: 0.425

Alfa AF: 0.438 Hom.: 18926

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
DANN	Benign	0.51

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

LitVar

Other links and lift over

dbSNP: rs3812570; hg19: chr9-139275204; COSMIC: COSV53731151; COSMIC: COSV53731151;