Variant 19-45064226-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_007056.3(CLASRP):c.1120C>T(p.Arg374Cys) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000328 in 1,586,266 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000034 ( 0 hom. )

Consequence

CLASRP
NM_007056.3 missense, splice_region

Scores

Splicing: ADA: 0.2462

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.46

Variant links:

Genes affected

CLASRP (HGNC:17731): (CLK4 associating serine/arginine rich protein) Predicted to be involved in RNA splicing and mRNA processing. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

CLASRP links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.33097857).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLASRP	NM_007056.3 linkuse as main transcript	c.1120C>T	p.Arg374Cys	missense_variant, splice_region_variant	12/21	ENST00000221455.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
CLASRP	ENST00000221455.8 linkuse as main transcript	c.1120C>T	p.Arg374Cys	missense_variant, splice_region_variant	12/21	1	NM_007056.3	P2
CLASRP	ENST00000391952.7 linkuse as main transcript	c.1120C>T	p.Arg374Cys	missense_variant, splice_region_variant, NMD_transcript_variant	12/21	1
CLASRP	ENST00000544944.6 linkuse as main transcript	c.1120C>T	p.Arg374Cys	missense_variant, splice_region_variant	11/19	2		A2
CLASRP	ENST00000391953.8 linkuse as main transcript	c.934C>T	p.Arg312Cys	missense_variant, splice_region_variant	11/20	2

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152138

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000387

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000526

AC:

AN:

189962

Hom.:

AF XY:

0.0000664

AC XY:

AN XY:

105376

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000349

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000207

Gnomad SAS exome

AF:

0.000220

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000342

AC:

AN:

1434010

Hom.:

Cov.:

AF XY:

0.0000450

AC XY:

AN XY:

711428

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000745

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000466

Gnomad4 SAS exome

AF:

0.000262

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000273

Gnomad4 OTH exome

AF:

0.0000506

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152256

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000388

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000336

Hom.:

Bravo

AF:

0.0000302

ExAC

AF:

0.0000347

AC:

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

Jul 06, 2021

The c.1120C>T (p.R374C) alteration is located in exon 12 (coding exon 11) of the CLASRP gene. This alteration results from a C to T substitution at nucleotide position 1120, causing the arginine (R) at amino acid position 374 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

Uncertain

0.44

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.30

Cadd

Pathogenic

Dann

Uncertain

1.0

DEOGEN2

Benign

0.075

T;.;.

Eigen

Benign

0.11

Eigen_PC

Benign

0.17

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.89

D;.;D

M_CAP

Pathogenic

0.62

MetaRNN

Benign

0.33

T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-2.0

N;N;N

REVEL

Benign

0.085

Sift

Uncertain

0.0010

D;D;D

Sift4G

Uncertain

0.024

D;D;D

Polyphen

0.91

.;.;P

Vest4

0.47

MutPred

0.29

Loss of methylation at R374 (P = 0.0534);.;Loss of methylation at R374 (P = 0.0534);

MVP

0.15

MPC

0.99

ClinPred

0.15

GERP RS

3.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

gMVP

0.63

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.25

dbscSNV1_RF

Benign

0.29

SpliceAI score (max)

0.10

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