rs3821116

chr2-168873339-G-T

Variant summary

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

The NM_020675.4(SPC25):c.550+246C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.395 in 151,974 control chromosomes in the GnomAD database, including 12,267 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 0.39 (12267 hom., cov: 32)
• Consequence: SPC25 NM_020675.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.680

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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.448 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPC25	NM_020675.4	c.550+246C>A		intron_variant		ENST00000282074.7
SPC25	XM_011511516.3	c.550+246C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPC25	ENST00000282074.7	c.550+246C>A		intron_variant		1	NM_020675.4	P1
SPC25	ENST00000479309.6	n.419+246C>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.395 AC: 59954 AN: 151854 Hom.: 12253 Cov.: 32

Gnomad AFR AF: 0.332

Gnomad AMI AF: 0.591

Gnomad AMR AF: 0.325

Gnomad ASJ AF: 0.378

Gnomad EAS AF: 0.271

Gnomad SAS AF: 0.295

Gnomad FIN AF: 0.465

Gnomad MID AF: 0.340

Gnomad NFE AF: 0.453

Gnomad OTH AF: 0.401

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

GnomAD4 genome AF: 0.395 AC: 60004 AN: 151974 Hom.: 12267 Cov.: 32 AF XY: 0.392 AC XY: 29105 AN XY: 74274

Gnomad4 AFR AF: 0.332

Gnomad4 AMR AF: 0.324

Gnomad4 ASJ AF: 0.378

Gnomad4 EAS AF: 0.272

Gnomad4 SAS AF: 0.295

Gnomad4 FIN AF: 0.465

Gnomad4 NFE AF: 0.453

Gnomad4 OTH AF: 0.405

Alfa AF: 0.435 Hom.: 28795

Bravo AF: 0.383

Asia WGS AF: 0.308 AC: 1069 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	0.50
Dann	Benign	0.51

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: rs3821116; hg19: chr2-169729849;