19-11145500-C-T

Position:

• chr19-11145500-C-T

Variant summary

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

The NM_182513.4(SPC24):​c.*1683G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.798 in 152,118 control chromosomes in the GnomAD database, including 48,918 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 0.80 (48909 hom., cov: 31)
  • Exomes 𝑓: 0.74 (9 hom.)
• Consequence: SPC24 NM_182513.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.285

Genes affected

SPC24 (HGNC:26913): (SPC24 component of NDC80 kinetochore complex) Predicted to be involved in cell division. Located in nucleolus and nucleoplasm. Part of Ndc80 complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.864 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPC24	NM_182513.4	c.*1683G>A		3_prime_UTR_variant	5/5	ENST00000592540.6	NP_872319.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPC24	ENST00000592540.6	c.*1683G>A		3_prime_UTR_variant	5/5	1	NM_182513.4	ENSP00000465075	P1
SPC24	ENST00000585567.5	c.435+2370G>A		intron_variant		3		ENSP00000468818

Frequencies

GnomAD3 genomes AF: 0.798 AC: 121332 AN: 151966 Hom.: 48881 Cov.: 31

Gnomad AFR AF: 0.691

Gnomad AMI AF: 0.776

Gnomad AMR AF: 0.876

Gnomad ASJ AF: 0.749

Gnomad EAS AF: 0.733

Gnomad SAS AF: 0.809

Gnomad FIN AF: 0.853

Gnomad MID AF: 0.832

Gnomad NFE AF: 0.844

Gnomad OTH AF: 0.836

GnomAD4 exome AF: 0.735 AC: 25 AN: 34 Hom.: 9 Cov.: 0 AF XY: 0.731 AC XY: 19 AN XY: 26

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 1.00

Gnomad4 ASJ exome AF: 0.500

Gnomad4 NFE exome AF: 0.808

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.798 AC: 121416 AN: 152084 Hom.: 48909 Cov.: 31 AF XY: 0.801 AC XY: 59510 AN XY: 74324

Gnomad4 AFR AF: 0.691

Gnomad4 AMR AF: 0.876

Gnomad4 ASJ AF: 0.749

Gnomad4 EAS AF: 0.732

Gnomad4 SAS AF: 0.808

Gnomad4 FIN AF: 0.853

Gnomad4 NFE AF: 0.844

Gnomad4 OTH AF: 0.833

Alfa AF: 0.829 Hom.: 24134

Bravo AF: 0.796

Asia WGS AF: 0.788 AC: 2739 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.14
DANN	Benign	0.57

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: rs4804146; hg19: chr19-11256176;