rs1764636014

Variant names:

• chr6-34767986-C-G
• rs1764636014
• NM_003093.3:c.239C>G

Your query was ambiguous. Multiple possible variants found:

• chr6-34767986-C-G
• chr6-34767986-C-T

Variant summary

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

The NM_003093.3(SNRPC):​c.239C>G​(p.Pro80Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,048 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P80L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SNRPC NM_003093.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.82
• Publications: 0 publications found

Genes affected

SNRPC (HGNC:11157): (small nuclear ribonucleoprotein polypeptide C) This gene encodes one of the specific protein components of the U1 small nuclear ribonucleoprotein (snRNP) particle required for the formation of the spliceosome. The encoded protein participates in the processing of nuclear precursor messenger RNA splicing. snRNP particles are attacked by autoantibodies frequently produced by patients with connective tissue diseases. The genome contains several pseudogenes of this functional gene. Alternative splicing results in a non-coding transcript variant.[provided by RefSeq, Oct 2009]

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_003093.3. 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
	SNRPC	NM_003093.3	MANE Select	c.239C>G	p.Pro80Arg	missense	Exon 4 of 6	NP_003084.1	P09234
	SNRPC	NR_029472.2		n.235C>G		non_coding_transcript_exon	Exon 3 of 5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNRPC	ENST00000244520.10	TSL:1 MANE Select	c.239C>G	p.Pro80Arg	missense	Exon 4 of 6	ENSP00000244520.5	P09234
	SNRPC	ENST00000374017.3	TSL:2	c.302C>G	p.Pro101Arg	missense	Exon 3 of 5	ENSP00000363129.3	A0A0A0MRR7
	SNRPC	ENST00000909265.1		c.239C>G	p.Pro80Arg	missense	Exon 4 of 7	ENSP00000579324.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460048 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 726394

African (AFR) AF: 0.00 AC: 0 AN: 33346

American (AMR) AF: 0.00 AC: 0 AN: 44344

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26106

East Asian (EAS) AF: 0.00 AC: 0 AN: 39630

South Asian (SAS) AF: 0.00 AC: 0 AN: 85892

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53352

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5746

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111334

Other (OTH) AF: 0.00 AC: 0 AN: 60298

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.87
BayesDel_addAF	Benign	-0.035	T
BayesDel_noAF	Benign	-0.29
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Benign	0.11	T
Eigen	Benign	0.12
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.011	T
MetaRNN	Uncertain	0.55	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L
PhyloP100		5.8
PrimateAI	Pathogenic	0.80	D
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.097
Sift	Benign	0.063	T
Sift4G	Benign	0.073	T
Polyphen		0.16	B
Vest4		0.67
MutPred		0.23		Loss of glycosylation at P80 (P = 0.003)
MVP		0.26
MPC		1.4
ClinPred		0.69	D
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.20
gMVP		0.84
Mutation Taster		=54/46	polymorphism

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: rs1764636014; hg19: chr6-34735763;