Variant 6-34770302-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.262C>T(p.Arg88Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000000686 in 1,458,414 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

SNRPC
NM_003093.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.82

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/exons	MANE	UniProt
SNRPC	NM_003093.3 linkuse as main transcript	c.262C>T	p.Arg88Cys	missense_variant	5/6	ENST00000244520.10
SNRPC	NR_029472.2 linkuse as main transcript	n.258C>T		non_coding_transcript_exon_variant	4/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
SNRPC	ENST00000244520.10 linkuse as main transcript	c.262C>T	p.Arg88Cys	missense_variant	5/6	1	NM_003093.3	P1
SNRPC	ENST00000374017.3 linkuse as main transcript	c.325C>T	p.Arg109Cys	missense_variant	4/5	2
SNRPC	ENST00000374018.5 linkuse as main transcript	c.139C>T	p.Arg47Cys	missense_variant	4/5	5
SNRPC	ENST00000474635.1 linkuse as main transcript	n.254C>T		non_coding_transcript_exon_variant	4/6	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.86e-7

AC:

AN:

1458414

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725836

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:

9.02e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Jan 04, 2024

The c.262C>T (p.R88C) 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 262, causing the arginine (R) at amino acid position 88 to be replaced by a cysteine (C). 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

Pathogenic

0.68

BayesDel_addAF

Pathogenic

0.18

BayesDel_noAF

Uncertain

0.020

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.013

T;.;T

Eigen

Uncertain

0.66

Eigen_PC

Uncertain

0.63

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.80

T;T;T

M_CAP

Benign

0.044

MetaRNN

Uncertain

0.51

D;D;D

MetaSVM

Benign

-0.49

MutationAssessor

Uncertain

2.3

M;.;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Pathogenic

0.90

PROVEAN

Benign

-2.3

N;D;N

REVEL

Benign

0.26

Sift

Uncertain

0.029

D;D;D

Sift4G

Benign

0.19

T;T;T

Polyphen

1.0

D;.;.

Vest4

0.64

MutPred

0.32

Loss of methylation at R88 (P = 0.0262);.;.;

MVP

0.49

MPC

1.7

ClinPred

0.92

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.25

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over