rs747819386

Variant names:

• chr20-20036323-G-A
• rs747819386
• NM_001278628.2:c.1936C>T

Your query was ambiguous. Multiple possible variants found:

• chr20-20036323-G-A
• chr20-20036323-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001278628.2(CRNKL1):​c.1936C>T​(p.Pro646Ser) 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 pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CRNKL1 NM_001278628.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.78

Genes affected

CRNKL1 (HGNC:15762): (crooked neck pre-mRNA splicing factor 1) The crooked neck (crn) gene of Drosophila is essential for embryogenesis and is thought to be involved in cell cycle progression and pre-mRNA splicing. A protein encoded by this human locus has been found to localize to pre-mRNA splicing complexes in the nucleus and is necessary for pre-mRNA splicing. Alternatively spliced transcript variants have been described. [provided by RefSeq, Jul 2013]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.785

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRNKL1	NM_001278628.2	c.1936C>T	p.Pro646Ser	missense_variant	Exon 14 of 14	ENST00000536226.2	NP_001265557.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRNKL1	ENST00000536226.2	c.1936C>T	p.Pro646Ser	missense_variant	Exon 14 of 14	1	NM_001278628.2	ENSP00000440733.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.95
BayesDel_addAF	Pathogenic	0.35	D
BayesDel_noAF	Pathogenic	0.27
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Benign	0.36	T;T;.
Eigen	Pathogenic	0.83
Eigen_PC	Pathogenic	0.81
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.89	D;D;D
M_CAP	Uncertain	0.12	D
MetaRNN	Pathogenic	0.79	D;D;D
MetaSVM	Uncertain	0.15	D
MutationAssessor	Pathogenic	3.1	.;M;.
PrimateAI	Uncertain	0.78	T
PROVEAN	Pathogenic	-6.9	D;D;D
REVEL	Pathogenic	0.81
Sift	Uncertain	0.0060	D;D;D
Sift4G	Uncertain	0.010	D;D;D
Polyphen		0.99	.;D;.
Vest4		0.45
MutPred		0.84		.;Loss of catalytic residue at P807 (P = 0.0429);.;
MVP		0.79
MPC		0.69
ClinPred		0.99	D
GERP RS		5.1
Varity_R		0.57
gMVP		0.73

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs747819386; hg19: chr20-20016967;