NM_007056.3:c.277A>C

Variant names:

• chr19-45052870-A-C
• rs766032837
• NM_007056.3:c.277A>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_007056.3(CLASRP):​c.277A>C​(p.Thr93Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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. T93S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: CLASRP NM_007056.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.65

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22258115).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLASRP	NM_007056.3	c.277A>C	p.Thr93Pro	missense_variant	Exon 4 of 21	ENST00000221455.8	NP_008987.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLASRP	ENST00000221455.8	c.277A>C	p.Thr93Pro	missense_variant	Exon 4 of 21	1	NM_007056.3	ENSP00000221455.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.073	T
BayesDel_noAF	Benign	-0.34
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0053	T;.
Eigen	Benign	-0.035
Eigen_PC	Benign	0.14
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Benign	0.77	T;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.22	T;T
MetaSVM	Benign	-1.1	T
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-0.59	N;N
REVEL	Benign	0.088
Sift	Benign	0.057	T;D
Sift4G	Benign	0.17	T;T
Polyphen		0.15	.;B
Vest4		0.40
MutPred		0.44		Gain of catalytic residue at T93 (P = 0.0046);Gain of catalytic residue at T93 (P = 0.0046);
MVP		0.12
MPC		1.0
ClinPred		0.89	D
GERP RS		4.4
gMVP		0.56

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs766032837; hg19: chr19-45556128;