2-233840987-T-G

Position:

• chr2-233840987-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018410.5(HJURP):​c.1793A>C​(p.Gln598Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: HJURP NM_018410.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -3.36

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]

ACMG classification

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=0.1278359).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HJURP	NM_018410.5	c.1793A>C	p.Gln598Pro	missense_variant	8/9	ENST00000411486.7	NP_060880.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HJURP	ENST00000411486.7	c.1793A>C	p.Gln598Pro	missense_variant	8/9	1	NM_018410.5	ENSP00000414109.1
HJURP	ENST00000432087.5	c.1631A>C	p.Gln544Pro	missense_variant	6/7	2		ENSP00000407208.1
HJURP	ENST00000441687.5	c.1538A>C	p.Gln513Pro	missense_variant	5/6	2		ENSP00000401944.1
HJURP	ENST00000414924.5	c.1538A>C	p.Gln513Pro	missense_variant	5/5	4		ENSP00000393253.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 12, 2023

The c.1793A>C (p.Q598P) alteration is located in exon 8 (coding exon 8) of the HJURP gene. This alteration results from a A to C substitution at nucleotide position 1793, causing the glutamine (Q) at amino acid position 598 to be replaced by a proline (P). 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	0.10
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	0.12
DANN	Benign	0.95
DEOGEN2	Benign	0.026	.;.;T;T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.45	T;T;T;T
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.13	T;T;T;T
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	2.0	.;.;M;.
PrimateAI	Benign	0.22	T
PROVEAN	Uncertain	-3.1	D;D;D;D
REVEL	Benign	0.11
Sift	Uncertain	0.012	D;D;D;D
Sift4G	Uncertain	0.025	D;D;D;D
Polyphen		0.11	B;B;B;.
Vest4		0.28
MutPred		0.42		.;.;Loss of sheet (P = 0.0357);.;
MVP		0.20
MPC		0.10
ClinPred		0.21	T
GERP RS		-2.9
Varity_R		0.29
gMVP		0.37

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-234749633;