rs150594731

Variant names:

• chr19-45052876-C-A
• rs150594731
• NM_007056.3:c.283C>A

Your query was ambiguous. Multiple possible variants found:

• chr19-45052876-C-A
• chr19-45052876-C-G
• chr19-45052876-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_007056.3(CLASRP):​c.283C>A​(p.Pro95Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 1,609,772 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P95A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000010 (0 hom.)
• Consequence: CLASRP NM_007056.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.37
• Publications: 1 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20584539).

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.283C>A	p.Pro95Thr	missense	Exon 4 of 21	NP_008987.2	Q8N2M8-1
	CLASRP	NM_001278439.2		c.127-235C>A		intron	N/A	NP_001265368.1	Q8N2M8-4
	CLASRP	NR_103529.2		n.376C>A		non_coding_transcript_exon	Exon 4 of 21

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLASRP	ENST00000221455.8	TSL:1 MANE Select	c.283C>A	p.Pro95Thr	missense	Exon 4 of 21	ENSP00000221455.3	Q8N2M8-1
	CLASRP	ENST00000391952.7	TSL:1	n.283C>A		non_coding_transcript_exon	Exon 4 of 21	ENSP00000375814.2	Q8N2M8-3
	CLASRP	ENST00000587112.1	TSL:1	n.226C>A		non_coding_transcript_exon	Exon 3 of 11	ENSP00000466371.1	K7EM61

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152082 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000284 AC: 7 AN: 246666 AF XY: 0.0000225

Gnomad AFR exome AF: 0.0000619

Gnomad AMR exome AF: 0.000121

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000894

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000103 AC: 15 AN: 1457690 Hom.: 0 Cov.: 31 AF XY: 0.00000965 AC XY: 7 AN XY: 725288

African (AFR) AF: 0.0000301 AC: 1 AN: 33226

American (AMR) AF: 0.0000691 AC: 3 AN: 43400

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25862

East Asian (EAS) AF: 0.00 AC: 0 AN: 39668

South Asian (SAS) AF: 0.0000233 AC: 2 AN: 85846

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53380

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5712

European-Non Finnish (NFE) AF: 0.00000811 AC: 9 AN: 1110414

Other (OTH) AF: 0.00 AC: 0 AN: 60182

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152082 Hom.: 0 Cov.: 31 AF XY: 0.0000269 AC XY: 2 AN XY: 74278

African (AFR) AF: 0.0000483 AC: 2 AN: 41398

American (AMR) AF: 0.00 AC: 0 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68002

Other (OTH) AF: 0.00 AC: 0 AN: 2080

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000227

ExAC AF: 0.0000165 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.031	T
Eigen	Uncertain	0.30
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-1.1	T
PhyloP100		3.4
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.039
Sift	Benign	0.053	T
Sift4G	Uncertain	0.013	D
Polyphen		0.97	D
Vest4		0.29
MutPred		0.29		Loss of catalytic residue at P94 (P = 0.0132)
MVP		0.082
MPC		1.1
ClinPred		0.21	T
GERP RS		4.4
gMVP		0.53
Mutation Taster		=70/30	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: rs150594731; hg19: chr19-45556134;