rs3821116

Variant names:

• chr2-168873339-G-T
• rs3821116
• NM_020675.4:c.550+246C>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SPC25	NM_020675.4	c.550+246C>A		intron_variant	Intron 6 of 6	ENST00000282074.7	NP_065726.1
SPC25	XM_011511516.3	c.550+246C>A		intron_variant	Intron 6 of 6		XP_011509818.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPC25	ENST00000282074.7	c.550+246C>A		intron_variant	Intron 6 of 6	1	NM_020675.4	ENSP00000282074.2
SPC25	ENST00000479309.6	n.419+246C>A		intron_variant	Intron 4 of 4	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

African (AFR) AF: 0.332 AC: 13777 AN: 41452

American (AMR) AF: 0.324 AC: 4942 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.378 AC: 1311 AN: 3468

East Asian (EAS) AF: 0.272 AC: 1409 AN: 5178

South Asian (SAS) AF: 0.295 AC: 1420 AN: 4816

European-Finnish (FIN) AF: 0.465 AC: 4903 AN: 10548

Middle Eastern (MID) AF: 0.332 AC: 97 AN: 292

European-Non Finnish (NFE) AF: 0.453 AC: 30750 AN: 67936

Other (OTH) AF: 0.405 AC: 856 AN: 2114

Alfa AF: 0.432 Hom.: 57313

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
PhyloP100		-0.68
Mutation Taster		=100/0	polymorphism (auto)

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: rs3821116; hg19: chr2-169729849;