rs13431652

Variant names:

• chr2-168896905-T-C
• rs13431652
• ENST00000451987.5:c.-172-6219A>G

Variant summary

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

The ENST00000451987.5(SPC25):​c.-172-6219A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 152,068 control chromosomes in the GnomAD database, including 4,880 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 0.24 (4880 hom., cov: 31)
• Consequence: SPC25 ENST00000451987.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.299

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 (NFE) allele frequency at 95% confidence interval = 0.304 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPC25	ENST00000451987.5	c.-172-6219A>G		intron_variant	Intron 1 of 4	3		ENSP00000393322.1
SPC25	ENST00000472216.2	n.177-6219A>G		intron_variant	Intron 1 of 5	5

Frequencies

GnomAD3 genomes AF: 0.243 AC: 36884 AN: 151950 Hom.: 4880 Cov.: 31

Gnomad AFR AF: 0.170

Gnomad AMI AF: 0.222

Gnomad AMR AF: 0.209

Gnomad ASJ AF: 0.217

Gnomad EAS AF: 0.0564

Gnomad SAS AF: 0.169

Gnomad FIN AF: 0.295

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.308

Gnomad OTH AF: 0.243

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

GnomAD4 genome AF: 0.243 AC: 36901 AN: 152068 Hom.: 4880 Cov.: 31 AF XY: 0.238 AC XY: 17682 AN XY: 74334

Gnomad4 AFR AF: 0.170

Gnomad4 AMR AF: 0.209

Gnomad4 ASJ AF: 0.217

Gnomad4 EAS AF: 0.0566

Gnomad4 SAS AF: 0.169

Gnomad4 FIN AF: 0.295

Gnomad4 NFE AF: 0.308

Gnomad4 OTH AF: 0.245

Alfa AF: 0.265 Hom.: 934

Bravo AF: 0.232

Asia WGS AF: 0.137 AC: 478 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	1.2
DANN	Benign	0.64

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs13431652; hg19: chr2-169753415;