rs524586

chr2-168881341-A-G

Variant summary

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

The NM_020675.4(SPC25):c.200-3957T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.57 in 152,064 control chromosomes in the GnomAD database, including 25,238 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 0.57 (25238 hom., cov: 32)
• Consequence: SPC25 NM_020675.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0830

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.68 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPC25	NM_020675.4	c.200-3957T>C		intron_variant		ENST00000282074.7
SPC25	XM_011511516.3	c.200-3957T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPC25	ENST00000282074.7	c.200-3957T>C		intron_variant		1	NM_020675.4	P1
SPC25	ENST00000451987.5	c.200-3957T>C		intron_variant		3
SPC25	ENST00000472216.2	n.607+3507T>C		intron_variant, non_coding_transcript_variant		5
SPC25	ENST00000479309.6	n.69-3957T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.570 AC: 86555 AN: 151946 Hom.: 25200 Cov.: 32

Gnomad AFR AF: 0.687

Gnomad AMI AF: 0.577

Gnomad AMR AF: 0.571

Gnomad ASJ AF: 0.556

Gnomad EAS AF: 0.619

Gnomad SAS AF: 0.660

Gnomad FIN AF: 0.498

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.501

Gnomad OTH AF: 0.547

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

GnomAD4 genome AF: 0.570 AC: 86642 AN: 152064 Hom.: 25238 Cov.: 32 AF XY: 0.574 AC XY: 42647 AN XY: 74352

Gnomad4 AFR AF: 0.687

Gnomad4 AMR AF: 0.572

Gnomad4 ASJ AF: 0.556

Gnomad4 EAS AF: 0.619

Gnomad4 SAS AF: 0.658

Gnomad4 FIN AF: 0.498

Gnomad4 NFE AF: 0.501

Gnomad4 OTH AF: 0.544

Alfa AF: 0.529 Hom.: 12138

Bravo AF: 0.580

Asia WGS AF: 0.659 AC: 2292 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	6.4
Dann	Benign	0.72

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: rs524586; hg19: chr2-169737851;