rs213551

Positions:

• chr2-233836743-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018410.5(HJURP):​c.*834T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.319 in 152,082 control chromosomes in the GnomAD database, including 8,609 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.32 (8609 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: HJURP NM_018410.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.259

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.489 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HJURP	NM_018410.5	c.*834T>C		3_prime_UTR_variant	9/9	ENST00000411486.7	NP_060880.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HJURP	ENST00000411486.7	c.*834T>C		3_prime_UTR_variant	9/9	1	NM_018410.5	ENSP00000414109	P2
HJURP	ENST00000432087.5	c.*834T>C		3_prime_UTR_variant	7/7	2		ENSP00000407208	A2
HJURP	ENST00000441687.5	c.*834T>C		3_prime_UTR_variant	6/6	2		ENSP00000401944	A2
HJURP	ENST00000433484.2	c.*300+534T>C		intron_variant, NMD_transcript_variant		5		ENSP00000395207

Frequencies

GnomAD3 genomes AF: 0.319 AC: 48520 AN: 151964 Hom.: 8604 Cov.: 32

Gnomad AFR AF: 0.175

Gnomad AMI AF: 0.474

Gnomad AMR AF: 0.335

Gnomad ASJ AF: 0.413

Gnomad EAS AF: 0.226

Gnomad SAS AF: 0.506

Gnomad FIN AF: 0.336

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.387

Gnomad OTH AF: 0.335

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.319 AC: 48543 AN: 152082 Hom.: 8609 Cov.: 32 AF XY: 0.322 AC XY: 23968 AN XY: 74336

Gnomad4 AFR AF: 0.175

Gnomad4 AMR AF: 0.336

Gnomad4 ASJ AF: 0.413

Gnomad4 EAS AF: 0.226

Gnomad4 SAS AF: 0.506

Gnomad4 FIN AF: 0.336

Gnomad4 NFE AF: 0.387

Gnomad4 OTH AF: 0.337

Alfa AF: 0.376 Hom.: 11233

Bravo AF: 0.312

Asia WGS AF: 0.400 AC: 1392 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.3
DANN	Benign	0.35

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: rs213551; hg19: chr2-234745389;