NM_022717.4:c.587C>A

Variant names:

• chr12-123466127-C-A
• rs146087320
• NM_022717.4:c.587C>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_022717.4(SNRNP35):​c.587C>A​(p.Ser196*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SNRNP35 NM_022717.4 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.29
• Publications: 0 publications found

Genes affected

SNRNP35 (HGNC:30852): (small nuclear ribonucleoprotein U11/U12 subunit 35) The protein encoded by this gene is a homolog of the U1-snRNP binding protein. The N-terminal half contains a RNA recognition motif and the C-terminal half is rich in Arg/Asp and Arg/Glu dipeptides, which is a characteristic of a variety of splicing factors. This protein is a component of the U11/U12 small nuclear ribonucleoproteins (snRNP) that form part of the U12-type spliceosome. Alternative splicing results in multiple transcript variants encoding two distinct isoforms and representing a non-protein coding variant. [provided by RefSeq, Aug 2013]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022717.4. 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
	SNRNP35	NM_022717.4	MANE Select	c.587C>A	p.Ser196*	stop_gained	Exon 2 of 2	NP_073208.1	Q16560-1
	SNRNP35	NM_180699.3		c.602C>A	p.Ser201*	stop_gained	Exon 2 of 2	NP_851030.1	Q16560-2
	SNRNP35	NR_104103.2		n.79-4965C>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNRNP35	ENST00000526639.3	TSL:1 MANE Select	c.587C>A	p.Ser196*	stop_gained	Exon 2 of 2	ENSP00000432595.2	Q16560-1
	SNRNP35	ENST00000412157.2	TSL:1	c.602C>A	p.Ser201*	stop_gained	Exon 2 of 2	ENSP00000403310.2	Q16560-2
	SNRNP35	ENST00000527158.2	TSL:1	n.99-4965C>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459874 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726164

African (AFR) AF: 0.00 AC: 0 AN: 33322

American (AMR) AF: 0.00 AC: 0 AN: 44254

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26038

East Asian (EAS) AF: 0.00 AC: 0 AN: 39684

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86028

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53388

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5750

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111114

Other (OTH) AF: 0.00 AC: 0 AN: 60296

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.57	D
BayesDel_noAF	Pathogenic	0.58
CADD	Pathogenic	36
DANN	Uncertain	0.99
Eigen	Uncertain	0.38
Eigen_PC	Benign	0.13
FATHMM_MKL	Uncertain	0.76	D
PhyloP100		3.3
Vest4		0.047
GERP RS		1.3
Mutation Taster		=42/158	disease causing

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

Other links and lift over

dbSNP: rs146087320; hg19: chr12-123950674;