19-45060597-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_007056.3(CLASRP):c.833G>A(p.Arg278Gln) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CLASRP NM_007056.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.97

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]

ACMG classification

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=0.30915374).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLASRP	NM_007056.3	c.833G>A	p.Arg278Gln	missense_variant	10/21	ENST00000221455.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLASRP	ENST00000221455.8	c.833G>A	p.Arg278Gln	missense_variant	10/21	1	NM_007056.3	P2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 21, 2023

The c.833G>A (p.R278Q) alteration is located in exon 10 (coding exon 9) of the CLASRP gene. This alteration results from a G to A substitution at nucleotide position 833, causing the arginine (R) at amino acid position 278 to be replaced by a glutamine (Q). 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	0.86
BayesDel_addAF	Uncertain	0.018	T
BayesDel_noAF	Benign	-0.21
Cadd	Pathogenic	33
Dann	Pathogenic	1.0
DEOGEN2	Benign	0.15	T;.;.
Eigen	Uncertain	0.62
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.96	D;.;D
M_CAP	Benign	0.033	D
MetaRNN	Benign	0.31	T;T;T
MetaSVM	Benign	-0.49	T
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.79	T
PROVEAN	Benign	-2.0	N;N;N
REVEL	Benign	0.14
Sift	Uncertain	0.015	D;D;D
Sift4G	Uncertain	0.037	D;D;D
Polyphen		1.0	.;.;D
Vest4		0.41
MutPred		0.30		Loss of methylation at R278 (P = 0.0446);.;Loss of methylation at R278 (P = 0.0446);
MVP		0.42
MPC		1.8
ClinPred		0.99	D
GERP RS		4.5
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.0
gMVP		0.72

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.

Other links and lift over

hg19: chr19-45563855;