19-45060428-G-T

Variant names:

• chr19-45060428-G-T
• rs754329851
• NM_007056.3:c.750G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_007056.3(CLASRP):​c.750G>T​(p.Lys250Asn) variant causes a missense change involving the alteration of a non-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: 32)
• Consequence: CLASRP NM_007056.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0320
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007056.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLASRP	NM_007056.3	MANE Select	c.750G>T	p.Lys250Asn	missense	Exon 9 of 21	NP_008987.2	Q8N2M8-1
	CLASRP	NM_001278439.2		c.564G>T	p.Lys188Asn	missense	Exon 8 of 20	NP_001265368.1	Q8N2M8-4
	CLASRP	NR_103529.2		n.843G>T		non_coding_transcript_exon	Exon 9 of 21

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLASRP	ENST00000221455.8	TSL:1 MANE Select	c.750G>T	p.Lys250Asn	missense	Exon 9 of 21	ENSP00000221455.3	Q8N2M8-1
	CLASRP	ENST00000391952.7	TSL:1	n.750G>T		non_coding_transcript_exon	Exon 9 of 21	ENSP00000375814.2	Q8N2M8-3
	CLASRP	ENST00000587112.1	TSL:1	n.*110G>T		non_coding_transcript_exon	Exon 8 of 11	ENSP00000466371.1	K7EM61

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.071	T
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.60
FATHMM_MKL	Benign	0.68	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.055	D
MetaRNN	Uncertain	0.47	T
MetaSVM	Benign	-0.75	T
PhyloP100		-0.032
PrimateAI	Pathogenic	0.92	D
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.19
Sift	Uncertain	0.010	D
Sift4G	Uncertain	0.013	D
Polyphen		1.0	D
Vest4		0.71
MutPred		0.20		Loss of ubiquitination at K250 (P = 0.0161)
MVP		0.32
MPC		1.8
ClinPred		0.99	D
GERP RS		-5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
gMVP		0.59
Mutation Taster		=67/33	polymorphism

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

Other links and lift over

dbSNP: rs754329851; hg19: chr19-45563686;