Genetic Variant NM_018410.5:c.1704A>C (chr2-233841076-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_018410.5(HJURP):c.1704A>C(p.Glu568Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00552 in 1,614,212 control chromosomes in the GnomAD database, including 284 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.014 ( 69 hom., cov: 32)

Exomes 𝑓: 0.0046 ( 215 hom. )

Consequence

HJURP
NM_018410.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.60

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]

HJURP links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0016310215).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0973 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HJURP	NM_018410.5 link	c.1704A>C	p.Glu568Asp	missense_variant	Exon 8 of 9	ENST00000411486.7	NP_060880.3	Q8NCD3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
HJURP	ENST00000411486.7 link	c.1704A>C	p.Glu568Asp	missense_variant	Exon 8 of 9	1	NM_018410.5	ENSP00000414109.1	Q8NCD3-1
HJURP	ENST00000432087.5 link	c.1542A>C	p.Glu514Asp	missense_variant	Exon 6 of 7	2		ENSP00000407208.1	Q8NCD3-2
HJURP	ENST00000441687.5 link	c.1449A>C	p.Glu483Asp	missense_variant	Exon 5 of 6	2		ENSP00000401944.1	Q8NCD3-3
HJURP	ENST00000414924.5 link	c.1449A>C	p.Glu483Asp	missense_variant	Exon 5 of 5	4		ENSP00000393253.1	C9JWC4

Frequencies

GnomAD3 genomes

AF:

0.0144

AC:

2198

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0350

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00432

Gnomad ASJ

AF:

0.000864

Gnomad EAS

AF:

0.105

Gnomad SAS

AF:

0.0139

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000367

Gnomad OTH

AF:

0.0167

GnomAD3 exomes

AF:

0.0122

AC:

3078

AN:

251484

Hom.:

126

AF XY:

0.0109

AC XY:

1483

AN XY:

135920

show subpopulations

Gnomad AFR exome

AF:

0.0366

Gnomad AMR exome

AF:

0.00188

Gnomad ASJ exome

AF:

0.000992

Gnomad EAS exome

AF:

0.114

Gnomad SAS exome

AF:

0.00869

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000193

Gnomad OTH exome

AF:

0.00505

GnomAD4 exome

AF:

0.00458

AC:

6696

AN:

1461888

Hom.:

215

Cov.:

AF XY:

0.00450

AC XY:

3276

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.0383

Gnomad4 AMR exome

AF:

0.00217

Gnomad4 ASJ exome

AF:

0.000995

Gnomad4 EAS exome

AF:

0.0885

Gnomad4 SAS exome

AF:

0.00980

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000284

Gnomad4 OTH exome

AF:

0.0101

GnomAD4 genome

AF:

0.0145

AC:

2208

AN:

152324

Hom.:

Cov.:

AF XY:

0.0146

AC XY:

1091

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.0351

Gnomad4 AMR

AF:

0.00431

Gnomad4 ASJ

AF:

0.000864

Gnomad4 EAS

AF:

0.105

Gnomad4 SAS

AF:

0.0143

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000367

Gnomad4 OTH

AF:

0.0198

Alfa

AF:

0.00588

Hom.:

Bravo

AF:

0.0170

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0352

AC:

155

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.0127

AC:

1547

Asia WGS

AF:

0.0680

AC:

238

AN:

3478

EpiCase

AF:

0.000436

EpiControl

AF:

0.000237

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.58

CADD

Benign

0.099

DANN

Benign

0.95

DEOGEN2

Benign

0.0036

.;.;T;T

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.059

LIST_S2

Benign

0.34

T;T;T;T

MetaRNN

Benign

0.0016

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

.;.;L;.

PrimateAI

Benign

0.24

PROVEAN

Benign

-1.3

N;N;N;N

REVEL

Benign

0.087

Sift

Benign

0.34

T;T;T;T

Sift4G

Benign

0.46

T;T;T;T

Polyphen

0.0090

B;B;B;.

Vest4

0.029

MutPred

0.050

.;.;Loss of methylation at K567 (P = 0.0786);.;

MPC

0.067

ClinPred

0.011

GERP RS

-8.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.030

gMVP

0.025

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over