Variant 2-233837641-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_018410.5(HJURP):c.2183C>T(p.Thr728Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000393 in 1,603,886 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000037 ( 0 hom. )

Consequence

HJURP
NM_018410.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0130

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.057204634).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HJURP	NM_018410.5 linkuse as main transcript	c.2183C>T	p.Thr728Met	missense_variant	9/9	ENST00000411486.7	NP_060880.3	Q8NCD3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
HJURP	ENST00000411486.7 linkuse as main transcript	c.2183C>T	p.Thr728Met	missense_variant	9/9	1	NM_018410.5	ENSP00000414109.1	Q8NCD3-1
HJURP	ENST00000433484.2 linkuse as main transcript	n.140C>T		non_coding_transcript_exon_variant	2/3	5		ENSP00000395207.1	H7C0I6
HJURP	ENST00000432087.5 linkuse as main transcript	c.2021C>T	p.Thr674Met	missense_variant	7/7	2		ENSP00000407208.1	Q8NCD3-2
HJURP	ENST00000441687.5 linkuse as main transcript	c.1928C>T	p.Thr643Met	missense_variant	6/6	2		ENSP00000401944.1	Q8NCD3-3

Frequencies

GnomAD3 genomes

AF:

0.0000593

AC:

AN:

151804

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000328

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000651

AC:

AN:

245818

Hom.:

AF XY:

0.0000902

AC XY:

AN XY:

133014

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000177

Gnomad ASJ exome

AF:

0.000700

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000180

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.0000372

AC:

AN:

1452082

Hom.:

Cov.:

AF XY:

0.0000443

AC XY:

AN XY:

722656

show subpopulations

Gnomad4 AFR exome

AF:

0.0000301

Gnomad4 AMR exome

AF:

0.000136

Gnomad4 ASJ exome

AF:

0.000537

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000280

Gnomad4 OTH exome

AF:

0.0000333

GnomAD4 genome

AF:

0.0000593

AC:

AN:

151804

Hom.:

Cov.:

AF XY:

0.0000405

AC XY:

AN XY:

74092

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.000328

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000180

Hom.:

Bravo

AF:

0.0000491

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.00000824

AC:

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

Apr 08, 2023

The c.2183C>T (p.T728M) alteration is located in exon 9 (coding exon 9) of the HJURP gene. This alteration results from a C to T substitution at nucleotide position 2183, causing the threonine (T) at amino acid position 728 to be replaced by a methionine (M). 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

-0.41

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.0067

.;.;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.018

LIST_S2

Benign

0.56

T;T;T

M_CAP

Benign

0.0020

MetaRNN

Benign

0.057

T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.90

.;.;L

PrimateAI

Benign

0.30

PROVEAN

Benign

-1.6

N;N;N

REVEL

Benign

0.23

Sift

Pathogenic

0.0

D;D;D

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

0.98

D;D;D

Vest4

0.11

MVP

0.085

MPC

0.090

ClinPred

0.061

GERP RS

-6.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.045

gMVP

0.055

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over