2-233841177-G-A

Variant summary

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

The NM_018410.5(HJURP):​c.1603C>T​(p.Arg535Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000192 in 1,614,090 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000019 ( 0 hom. )

Consequence

HJURP
NM_018410.5 missense

Scores

1
3
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.175
Variant links:
Genes affected
HJURP (HGNC:25444): (Holliday junction recognition protein) Enables histone binding activity and identical protein binding activity. Involved in several processes, including CENP-A containing chromatin assembly; regulation of DNA binding activity; and regulation of protein-containing complex assembly. Located in kinetochore; mitochondrion; and nuclear lumen. [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=0.093141675).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
HJURPNM_018410.5 linkc.1603C>T p.Arg535Cys missense_variant 8/9 ENST00000411486.7 NP_060880.3 Q8NCD3-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
HJURPENST00000411486.7 linkc.1603C>T p.Arg535Cys missense_variant 8/91 NM_018410.5 ENSP00000414109.1 Q8NCD3-1
HJURPENST00000432087.5 linkc.1441C>T p.Arg481Cys missense_variant 6/72 ENSP00000407208.1 Q8NCD3-2
HJURPENST00000441687.5 linkc.1348C>T p.Arg450Cys missense_variant 5/62 ENSP00000401944.1 Q8NCD3-3
HJURPENST00000414924.5 linkc.1348C>T p.Arg450Cys missense_variant 5/54 ENSP00000393253.1 C9JWC4

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152204
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000192
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000239
AC:
6
AN:
251476
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135912
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000163
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000264
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000192
AC:
28
AN:
1461886
Hom.:
0
Cov.:
35
AF XY:
0.0000165
AC XY:
12
AN XY:
727244
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000504
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000225
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152204
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74354
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000192
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000312
Hom.:
0
ExAC
AF:
0.0000247
AC:
3

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 GeneticsDec 13, 2023The c.1603C>T (p.R535C) alteration is located in exon 8 (coding exon 8) of the HJURP gene. This alteration results from a C to T substitution at nucleotide position 1603, causing the arginine (R) at amino acid position 535 to be replaced by a cysteine (C). 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
0.097
BayesDel_addAF
Benign
-0.48
T
BayesDel_noAF
Benign
-0.66
CADD
Benign
12
DANN
Uncertain
1.0
DEOGEN2
Benign
0.025
.;.;T;T
Eigen
Benign
-0.80
Eigen_PC
Benign
-0.91
FATHMM_MKL
Benign
0.17
N
LIST_S2
Benign
0.68
T;T;T;T
M_CAP
Benign
0.0049
T
MetaRNN
Benign
0.093
T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.4
.;.;L;.
PrimateAI
Benign
0.20
T
PROVEAN
Pathogenic
-4.8
D;D;D;D
REVEL
Benign
0.12
Sift
Uncertain
0.0020
D;D;D;D
Sift4G
Uncertain
0.0020
D;D;D;D
Polyphen
0.25
B;B;B;.
Vest4
0.079
MutPred
0.26
.;.;Loss of phosphorylation at S532 (P = 0.0637);.;
MVP
0.16
MPC
0.20
ClinPred
0.17
T
GERP RS
0.26
Varity_R
0.11
gMVP
0.062

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: rs545856531; hg19: chr2-234749823; COSMIC: COSV64979688; COSMIC: COSV64979688; API