20-20037528-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001278628.2(CRNKL1):​c.1691A>G​(p.Glu564Gly) 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

CRNKL1
NM_001278628.2 missense

Scores

1
5
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.08
Variant links:
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]

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ACMG classification

Classification made for transcript

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=0.2070725).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CRNKL1NM_001278628.2 linkuse as main transcriptc.1691A>G p.Glu564Gly missense_variant 13/14 ENST00000536226.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CRNKL1ENST00000536226.2 linkuse as main transcriptc.1691A>G p.Glu564Gly missense_variant 13/141 NM_001278628.2 P1Q9BZJ0-2

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
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJan 31, 2023The c.2174A>G (p.E725G) alteration is located in exon 14 (coding exon 14) of the CRNKL1 gene. This alteration results from a A to G substitution at nucleotide position 2174, causing the glutamic acid (E) at amino acid position 725 to be replaced by a glycine (G). 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
Benign
0.11
BayesDel_addAF
Benign
-0.035
T
BayesDel_noAF
Benign
-0.29
CADD
Benign
22
DANN
Uncertain
1.0
DEOGEN2
Benign
0.060
T;T;.
Eigen
Benign
0.0067
Eigen_PC
Benign
0.18
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Benign
0.60
T;T;T
M_CAP
Benign
0.0073
T
MetaRNN
Benign
0.21
T;T;T
MetaSVM
Benign
-0.99
T
MutationAssessor
Uncertain
2.2
.;M;.
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Benign
0.42
T
PROVEAN
Uncertain
-3.5
D;D;D
REVEL
Benign
0.11
Sift
Uncertain
0.019
D;D;T
Sift4G
Uncertain
0.050
T;D;T
Polyphen
0.0040
.;B;.
Vest4
0.38
MutPred
0.31
.;Gain of glycosylation at S722 (P = 0.0479);.;
MVP
0.38
MPC
0.32
ClinPred
0.97
D
GERP RS
5.0
Varity_R
0.38
gMVP
0.31

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs111503447; hg19: chr20-20018172; COSMIC: COSV100131415; COSMIC: COSV100131415; API