20-20039670-A-G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001278628.2(CRNKL1):ā€‹c.1484T>Cā€‹(p.Ile495Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000114 in 1,614,068 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000092 ( 0 hom., cov: 32)
Exomes š‘“: 0.00012 ( 0 hom. )

Consequence

CRNKL1
NM_001278628.2 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.97
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.07014501).
BS2
High AC in GnomAd4 at 14 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CRNKL1NM_001278628.2 linkuse as main transcriptc.1484T>C p.Ile495Thr missense_variant 11/14 ENST00000536226.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CRNKL1ENST00000536226.2 linkuse as main transcriptc.1484T>C p.Ile495Thr missense_variant 11/141 NM_001278628.2 P1Q9BZJ0-2

Frequencies

GnomAD3 genomes
AF:
0.0000920
AC:
14
AN:
152186
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000724
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000994
AC:
25
AN:
251426
Hom.:
0
AF XY:
0.000125
AC XY:
17
AN XY:
135882
show subpopulations
Gnomad AFR exome
AF:
0.0000615
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000229
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000141
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.000116
AC:
170
AN:
1461882
Hom.:
0
Cov.:
32
AF XY:
0.000122
AC XY:
89
AN XY:
727238
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.0000447
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000151
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000128
Gnomad4 OTH exome
AF:
0.000199
GnomAD4 genome
AF:
0.0000920
AC:
14
AN:
152186
Hom.:
0
Cov.:
32
AF XY:
0.000108
AC XY:
8
AN XY:
74344
show subpopulations
Gnomad4 AFR
AF:
0.0000724
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000134
Hom.:
0
Bravo
AF:
0.0000869
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.00
AC:
0
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.000107
AC:
13
EpiCase
AF:
0.00
EpiControl
AF:
0.000178

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 GeneticsMar 07, 2024The c.1967T>C (p.I656T) alteration is located in exon 12 (coding exon 12) of the CRNKL1 gene. This alteration results from a T to C substitution at nucleotide position 1967, causing the isoleucine (I) at amino acid position 656 to be replaced by a threonine (T). 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
0.058
BayesDel_addAF
Benign
-0.41
T
BayesDel_noAF
Benign
-0.54
CADD
Benign
17
DANN
Benign
0.75
DEOGEN2
Benign
0.0068
T;T;.
Eigen
Benign
-0.31
Eigen_PC
Benign
-0.041
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Uncertain
0.92
D;D;D
M_CAP
Benign
0.0048
T
MetaRNN
Benign
0.070
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
-0.59
.;N;.
MutationTaster
Benign
0.81
D;D;D
PrimateAI
Uncertain
0.69
T
PROVEAN
Benign
-0.11
N;N;N
REVEL
Benign
0.076
Sift
Benign
0.71
T;T;T
Sift4G
Benign
0.59
T;T;T
Polyphen
0.0040
.;B;.
Vest4
0.38
MVP
0.20
MPC
0.34
ClinPred
0.052
T
GERP RS
5.8
Varity_R
0.066
gMVP
0.24

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

Publications

LitVar

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

Other links and lift over

dbSNP: rs149517251; hg19: chr20-20020314; API