2-233841076-T-A

Position:

• chr2-233841076-T-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_018410.5(HJURP):​c.1704A>T​(p.Glu568Asp) 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. 16/21 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 same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency: Genomes: not found (cov: 32)
• Consequence: HJURP NM_018410.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.60

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 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=0.04757017).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HJURP	NM_018410.5	c.1704A>T	p.Glu568Asp	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.1704A>T	p.Glu568Asp	missense_variant	8/9	1	NM_018410.5	ENSP00000414109	P2
HJURP	ENST00000432087.5	c.1542A>T	p.Glu514Asp	missense_variant	6/7	2		ENSP00000407208	A2
HJURP	ENST00000441687.5	c.1449A>T	p.Glu483Asp	missense_variant	5/6	2		ENSP00000401944	A2
HJURP	ENST00000414924.5	c.1449A>T	p.Glu483Asp	missense_variant	5/5	4		ENSP00000393253

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	0.096
DANN	Benign	0.95
DEOGEN2	Benign	0.0036	.;.;T;T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.063	N
LIST_S2	Benign	0.34	T;T;T;T
M_CAP	Benign	0.0060	T
MetaRNN	Benign	0.048	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	.;.;L;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.24	T
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);.;
MVP		0.15
MPC		0.067
ClinPred		0.11	T
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

Other links and lift over

dbSNP: rs3771333; hg19: chr2-234749722;