rs3771333

Variant names:

• chr2-233841076-T-A
• rs3771333
• NM_018410.5:c.1704A>T

Your query was ambiguous. Multiple possible variants found:

• chr2-233841076-T-A
• chr2-233841076-T-C
• chr2-233841076-T-G

Variant summary

Our verdict is Likely benign. The variant received -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. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: HJURP NM_018410.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.60
• Publications: 19 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04757017).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018410.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HJURP	NM_018410.5	MANE Select	c.1704A>T	p.Glu568Asp	missense	Exon 8 of 9	NP_060880.3
	HJURP	NM_001282962.2		c.1542A>T	p.Glu514Asp	missense	Exon 6 of 7	NP_001269891.1	Q8NCD3-2
	HJURP	NM_001282963.2		c.1449A>T	p.Glu483Asp	missense	Exon 5 of 6	NP_001269892.1	Q8NCD3-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HJURP	ENST00000411486.7	TSL:1 MANE Select	c.1704A>T	p.Glu568Asp	missense	Exon 8 of 9	ENSP00000414109.1	Q8NCD3-1
	HJURP	ENST00000432087.5	TSL:2	c.1542A>T	p.Glu514Asp	missense	Exon 6 of 7	ENSP00000407208.1	Q8NCD3-2
	HJURP	ENST00000441687.5	TSL:2	c.1449A>T	p.Glu483Asp	missense	Exon 5 of 6	ENSP00000401944.1	Q8NCD3-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.063	N
LIST_S2	Benign	0.34	T
M_CAP	Benign	0.0060	T
MetaRNN	Benign	0.048	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L
PhyloP100		-2.6
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.087
Sift	Benign	0.34	T
Sift4G	Benign	0.46	T
Polyphen		0.0090	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
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs3771333; hg19: chr2-234749722;