Variant chr19-45064420-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000221455.8(CLASRP):c.1199C>T(p.Ser400Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000726 in 1,377,268 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 7.3e-7 ( 0 hom. )

Consequence

CLASRP
ENST00000221455.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.487

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.17490879).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLASRP	NM_007056.3 linkuse as main transcript	c.1199C>T	p.Ser400Phe	missense_variant	13/21	ENST00000221455.8	NP_008987.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
CLASRP	ENST00000221455.8 linkuse as main transcript	c.1199C>T	p.Ser400Phe	missense_variant	13/21	1	NM_007056.3	ENSP00000221455	P2
CLASRP	ENST00000391952.7 linkuse as main transcript	c.1199C>T	p.Ser400Phe	missense_variant, NMD_transcript_variant	13/21	1		ENSP00000375814
CLASRP	ENST00000544944.6 linkuse as main transcript	c.1199C>T	p.Ser400Phe	missense_variant	12/19	2		ENSP00000438702	A2
CLASRP	ENST00000391953.8 linkuse as main transcript	c.1013C>T	p.Ser338Phe	missense_variant	12/20	2		ENSP00000375815

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.26e-7

AC:

AN:

1377268

Hom.:

Cov.:

AF XY:

0.00000147

AC XY:

AN XY:

680006

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:

9.33e-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

Jul 20, 2021

The c.1199C>T (p.S400F) alteration is located in exon 13 (coding exon 12) of the CLASRP gene. This alteration results from a C to T substitution at nucleotide position 1199, causing the serine (S) at amino acid position 400 to be replaced by a phenylalanine (F). 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

0.41

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.082

T;.;.

Eigen

Benign

-0.42

Eigen_PC

Benign

-0.26

FATHMM_MKL

Benign

0.57

LIST_S2

Benign

0.83

T;.;T

M_CAP

Benign

0.064

MetaRNN

Benign

0.17

T;T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Pathogenic

0.88

PROVEAN

Uncertain

-2.7

D;D;D

REVEL

Benign

0.23

Sift

Uncertain

0.013

D;D;D

Sift4G

Uncertain

0.0050

D;D;D

Polyphen

0.0

.;.;B

Vest4

0.38

MutPred

0.32

Loss of phosphorylation at S400 (P = 0);.;Loss of phosphorylation at S400 (P = 0);

MVP

0.25

MPC

0.80

ClinPred

0.83

GERP RS

3.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

gMVP

0.55

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