20-20039839-T-C
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Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2
The NM_001278628.2(CRNKL1):āc.1315A>Gā(p.Ile439Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000298 in 1,613,438 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.000013 ( 0 hom., cov: 32)
Exomes š: 0.000031 ( 0 hom. )
Consequence
CRNKL1
NM_001278628.2 missense
NM_001278628.2 missense
Scores
2
7
10
Clinical Significance
Conservation
PhyloP100: 7.83
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 Likely_benign. Variant got -5 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.34205005).
BS2
High AC in GnomAdExome4 at 46 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CRNKL1 | NM_001278628.2 | c.1315A>G | p.Ile439Val | missense_variant | 11/14 | ENST00000536226.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CRNKL1 | ENST00000536226.2 | c.1315A>G | p.Ile439Val | missense_variant | 11/14 | 1 | NM_001278628.2 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152250Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000240 AC: 6AN: 249832Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135380
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GnomAD4 exome AF: 0.0000315 AC: 46AN: 1461188Hom.: 0 Cov.: 32 AF XY: 0.0000261 AC XY: 19AN XY: 726938
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GnomAD4 genome AF: 0.0000131 AC: 2AN: 152250Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74392
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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 submitter | clinical testing | Ambry Genetics | Dec 27, 2023 | The c.1798A>G (p.I600V) alteration is located in exon 12 (coding exon 12) of the CRNKL1 gene. This alteration results from a A to G substitution at nucleotide position 1798, causing the isoleucine (I) at amino acid position 600 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Pathogenic
.;M;.
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N
REVEL
Benign
Sift
Uncertain
D;D;D
Sift4G
Uncertain
D;D;D
Polyphen
0.11
.;B;.
Vest4
MutPred
0.69
.;Loss of catalytic residue at I600 (P = 0.1253);.;
MVP
MPC
0.33
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at