rs573225

chr2-168901031-G-Achr2-168901031-G-C

Variant summary

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

The ENST00000451987.5(SPC25):c.-172-10345C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.778 in 152,224 control chromosomes in the GnomAD database, including 46,938 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 0.78 (46938 hom., cov: 33)
• Consequence: SPC25 ENST00000451987.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.69

Genes affected

SPC25 (HGNC:24031): (SPC25 component of NDC80 kinetochore complex) This gene encodes a protein that may be involved in kinetochore-microtubule interaction and spindle checkpoint activity. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.913 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPC25	ENST00000451987.5	c.-172-10345C>T		intron_variant		3
SPC25	ENST00000472216.2	n.177-10345C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.778 AC: 118274 AN: 152106 Hom.: 46875 Cov.: 33

Gnomad AFR AF: 0.921

Gnomad AMI AF: 0.773

Gnomad AMR AF: 0.790

Gnomad ASJ AF: 0.767

Gnomad EAS AF: 0.931

Gnomad SAS AF: 0.830

Gnomad FIN AF: 0.703

Gnomad MID AF: 0.731

Gnomad NFE AF: 0.685

Gnomad OTH AF: 0.767

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.778 AC: 118398 AN: 152224 Hom.: 46938 Cov.: 33 AF XY: 0.782 AC XY: 58154 AN XY: 74404

Gnomad4 AFR AF: 0.921

Gnomad4 AMR AF: 0.790

Gnomad4 ASJ AF: 0.767

Gnomad4 EAS AF: 0.930

Gnomad4 SAS AF: 0.830

Gnomad4 FIN AF: 0.703

Gnomad4 NFE AF: 0.685

Gnomad4 OTH AF: 0.765

Alfa AF: 0.709 Hom.: 27805

Bravo AF: 0.792

Asia WGS AF: 0.857 AC: 2981 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
Cadd	Benign	16
Dann	Benign	0.51

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs573225; hg19: chr2-169757541;