chr15-101292483-T-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 publications found

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]

PCSK6 Gene-Disease associations (from GenCC):

• congenital heart disease

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003090.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNRPA1	NM_003090.4	MANE Select	c.231-443A>G		intron	N/A	NP_003081.2	P09661
	SNRPA1	NR_135506.2		n.152+2614A>G		intron	N/A
	SNRPA1	NR_135507.2		n.152+2614A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNRPA1	ENST00000254193.11	TSL:1 MANE Select	c.231-443A>G		intron	N/A	ENSP00000254193.6	P09661
	SNRPA1	ENST00000394082.8	TSL:1	n.107+2614A>G		intron	N/A
	SNRPA1	ENST00000540017.6	TSL:1	n.159+2614A>G		intron	N/A

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

African (AFR) AF: 0.251 AC: 10394 AN: 41426

American (AMR) AF: 0.374 AC: 5709 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.343 AC: 1190 AN: 3470

East Asian (EAS) AF: 0.265 AC: 1370 AN: 5178

South Asian (SAS) AF: 0.349 AC: 1675 AN: 4806

European-Finnish (FIN) AF: 0.291 AC: 3067 AN: 10524

Middle Eastern (MID) AF: 0.370 AC: 108 AN: 292

European-Non Finnish (NFE) AF: 0.343 AC: 23321 AN: 67964

Other (OTH) AF: 0.329 AC: 692 AN: 2106

Alfa AF: 0.335 Hom.: 4634

Bravo AF: 0.318

Asia WGS AF: 0.284 AC: 987 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	9.3
DANN	Benign	0.84
PhyloP100		-0.057
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4965818; hg19: chr15-101832688;