rs3812571

Positions:

• chr9-136380842-G-A
• chr9-136380842-G-C

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_003086.4(SNAPC4):​c.2397C>T​(p.His799=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,448,030 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SNAPC4 NM_003086.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.214

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 Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP7: Synonymous conserved (PhyloP=0.214 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SNAPC4	NM_003086.4	c.2397C>T	p.His799=	synonymous_variant	20/24	ENST00000684778.1	NP_003077.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SNAPC4	ENST00000684778.1	c.2397C>T	p.His799=	synonymous_variant	20/24		NM_003086.4	ENSP00000510559	P1
SNAPC4	ENST00000298532.2	c.2397C>T	p.His799=	synonymous_variant	19/23	1		ENSP00000298532	P1
SNAPC4	ENST00000637388.2	c.2397C>T	p.His799=	synonymous_variant	20/24	5		ENSP00000490037	P1
SNAPC4	ENST00000689006.1	c.*1610C>T		3_prime_UTR_variant, NMD_transcript_variant	20/24			ENSP00000509362

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1448030 Hom.: 0 Cov.: 29 AF XY: 0.00000139 AC XY: 1 AN XY: 721188

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000182

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	5.3
DANN	Benign	0.63

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: rs3812571; hg19: chr9-139275294;