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GeneBe

10-24209252-G-A

Variant summary

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

The NM_019590.5(KIAA1217):c.59G>A(p.Arg20Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,236 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 (★).

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

KIAA1217
NM_019590.5 missense

Scores

1
3
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.00
Variant links:
Genes affected
KIAA1217 (HGNC:25428): (KIAA1217) Predicted to be involved in embryonic skeletal system development. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

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=0.091941744).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
KIAA1217NM_019590.5 linkuse as main transcriptc.59G>A p.Arg20Lys missense_variant 1/21 ENST00000376454.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
KIAA1217ENST00000376454.8 linkuse as main transcriptc.59G>A p.Arg20Lys missense_variant 1/211 NM_019590.5 A2Q5T5P2-1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
AF:
0.00000547
AC:
8
AN:
1461236
Hom.:
0
Cov.:
30
AF XY:
0.00000275
AC XY:
2
AN XY:
727010
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000720
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
31

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 GeneticsAug 03, 2022The c.59G>A (p.R20K) alteration is located in exon 1 (coding exon 1) of the KIAA1217 gene. This alteration results from a G to A substitution at nucleotide position 59, causing the arginine (R) at amino acid position 20 to be replaced by a lysine (K). 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
0.13
BayesDel_addAF
Benign
-0.15
T
BayesDel_noAF
Benign
-0.46
Cadd
Benign
22
Dann
Uncertain
0.99
DEOGEN2
Benign
0.016
T;.;.;T;.
Eigen
Benign
-0.41
Eigen_PC
Benign
-0.28
FATHMM_MKL
Uncertain
0.79
D
LIST_S2
Uncertain
0.86
D;D;D;D;D
M_CAP
Benign
0.0099
T
MetaRNN
Benign
0.092
T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationTaster
Benign
1.0
D;N;N;N
PrimateAI
Benign
0.42
T
PROVEAN
Benign
-0.54
N;N;N;N;.
REVEL
Benign
0.046
Sift
Benign
0.067
T;D;.;T;.
Sift4G
Pathogenic
0.0
D;D;D;D;D
Polyphen
0.073, 0.22
.;B;.;B;.
Vest4
0.19, 0.18, 0.37
MutPred
0.19
Gain of ubiquitination at R20 (P = 0.0018);Gain of ubiquitination at R20 (P = 0.0018);Gain of ubiquitination at R20 (P = 0.0018);Gain of ubiquitination at R20 (P = 0.0018);Gain of ubiquitination at R20 (P = 0.0018);
MVP
0.37
MPC
0.19
ClinPred
0.53
D
GERP RS
3.2
Varity_R
0.14
gMVP
0.15

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-24498181; API