NM_003090.4:c.231-443A>G

Variant names:

• chr15-101292483-T-C
• rs4965818
• NM_003090.4:c.231-443A>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003090.4(SNRPA1):​c.231-443A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.314 in 151,950 control chromosomes in the GnomAD database, including 7,648 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 0.31 (7648 hom., cov: 32)
• Consequence: SNRPA1 NM_003090.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0570

Genes affected

SNRPA1 (HGNC:11152): (small nuclear ribonucleoprotein polypeptide A') Enables RNA binding activity. Involved in mRNA splicing, via spliceosome and spermatogenesis. Located in nuclear speck. Part of U2-type catalytic step 2 spliceosome and U2-type precatalytic spliceosome. Implicated in connective tissue disease. [provided by Alliance of Genome Resources, Apr 2022]

PCSK6 (HGNC:8569): (proprotein convertase subtilisin/kexin type 6) This gene encodes a member of the subtilisin-like proprotein convertase family, which includes proteases that process protein and peptide precursors trafficking through regulated or constitutive branches of the secretory pathway. The encoded protein undergoes an initial autocatalytic processing event in the ER to generate a heterodimer which exits the ER and sorts to the trans-Golgi network where a second autocatalytic event takes place and the catalytic activity is acquired. The encoded protease is constitutively secreted into the extracellular matrix and expressed in many tissues, including neuroendocrine, liver, gut, and brain. This gene encodes one of the seven basic amino acid-specific members which cleave their substrates at single or paired basic residues. Some of its substrates include transforming growth factor beta related proteins, proalbumin, and von Willebrand factor. This gene is thought to play a role in tumor progression and left-right patterning. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Feb 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.366 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SNRPA1	NM_003090.4	c.231-443A>G		intron_variant	Intron 2 of 8	ENST00000254193.11	NP_003081.2
SNRPA1	NR_135506.2	n.152+2614A>G		intron_variant	Intron 1 of 5
SNRPA1	NR_135507.2	n.152+2614A>G		intron_variant	Intron 1 of 4
SNRPA1	NR_135508.2	n.301-443A>G		intron_variant	Intron 2 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SNRPA1	ENST00000254193.11	c.231-443A>G		intron_variant	Intron 2 of 8	1	NM_003090.4	ENSP00000254193.6

Frequencies

GnomAD3 genomes AF: 0.314 AC: 47656 AN: 151834 Hom.: 7641 Cov.: 32

Gnomad AFR AF: 0.251

Gnomad AMI AF: 0.182

Gnomad AMR AF: 0.374

Gnomad ASJ AF: 0.343

Gnomad EAS AF: 0.264

Gnomad SAS AF: 0.346

Gnomad FIN AF: 0.291

Gnomad MID AF: 0.369

Gnomad NFE AF: 0.343

Gnomad OTH AF: 0.332

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.314 AC: 47692 AN: 151950 Hom.: 7648 Cov.: 32 AF XY: 0.313 AC XY: 23241 AN XY: 74254

Gnomad4 AFR AF: 0.251

Gnomad4 AMR AF: 0.374

Gnomad4 ASJ AF: 0.343

Gnomad4 EAS AF: 0.265

Gnomad4 SAS AF: 0.349

Gnomad4 FIN AF: 0.291

Gnomad4 NFE AF: 0.343

Gnomad4 OTH AF: 0.329

Alfa AF: 0.336 Hom.: 4182

Bravo AF: 0.318

Asia WGS AF: 0.284 AC: 987 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	9.3
DANN	Benign	0.84

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs4965818; hg19: chr15-101832688;