Variant 6-34770305-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_003093.3(SNRPC):c.265C>T(p.Pro89Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SNRPC
NM_003093.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.65

Variant links:

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]

SNRPC links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SNRPC	NM_003093.3 link	c.265C>T	p.Pro89Ser	missense_variant	Exon 5 of 6	ENST00000244520.10	NP_003084.1	P09234Q5TAL4
SNRPC	NR_029472.2 link	n.261C>T		non_coding_transcript_exon_variant	Exon 4 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SNRPC	ENST00000244520.10 link	c.265C>T	p.Pro89Ser	missense_variant	Exon 5 of 6	1	NM_003093.3	ENSP00000244520.5	P09234
SNRPC	ENST00000374017.3 link	c.328C>T	p.Pro110Ser	missense_variant	Exon 4 of 5	2		ENSP00000363129.3	A0A0A0MRR7
SNRPC	ENST00000374018.5 link	c.142C>T	p.Pro48Ser	missense_variant	Exon 4 of 5	5		ENSP00000363130.1	Q5TAL2
SNRPC	ENST00000474635.1 link	n.257C>T		non_coding_transcript_exon_variant	Exon 4 of 6	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

6.85e-7

AC:

AN:

1459810

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726412

show subpopulations

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:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000936

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 15, 2023

The c.265C>T (p.P89S) alteration is located in exon 5 (coding exon 5) of the SNRPC gene. This alteration results from a C to T substitution at nucleotide position 265, causing the proline (P) at amino acid position 89 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_addAF

Pathogenic

0.18

BayesDel_noAF

Uncertain

0.020

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.12

T;.;T

Eigen

Pathogenic

0.70

Eigen_PC

Pathogenic

0.69

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.86

D;T;D

M_CAP

Benign

0.046

MetaRNN

Uncertain

0.56

D;D;D

MetaSVM

Benign

-0.43

MutationAssessor

Uncertain

2.5

M;.;.

PrimateAI

Pathogenic

0.86

PROVEAN

Uncertain

-3.0

D;D;D

REVEL

Uncertain

0.46

Sift

Benign

0.077

T;T;T

Sift4G

Benign

0.088

T;T;T

Polyphen

0.99

D;.;.

Vest4

0.64

MutPred

0.31

Gain of phosphorylation at P89 (P = 0.0033);.;.;

MVP

0.60

MPC

1.4

ClinPred

0.96

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.26

gMVP

0.75

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over