10-75368242-C-T

Variant names:

• chr10-75368242-C-T
• rs1259590
• ENST00000418818.6:n.142+32863G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000418818.6(ENSG00000270087):​n.142+32863G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.5 in 151,998 control chromosomes in the GnomAD database, including 20,347 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 0.50 (20347 hom., cov: 32)
• Consequence: ENSG00000270087 ENST00000418818.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0760
• Publications: 3 publications found

Genes affected

ENSG00000270087 (HGNC:):

ZNF503-AS1 (HGNC:27370): (ZNF503 antisense RNA 1)

ZNF503 (HGNC:23589): (zinc finger protein 503) Predicted to enable metal ion binding activity. Involved in G1 to G0 transition involved in cell differentiation; negative regulation of cell population proliferation; and negative regulation of gene expression. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.613 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF503	NR_120651.2	n.812+32863G>A		intron_variant	Intron 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000270087	ENST00000418818.6	n.142+32863G>A		intron_variant	Intron 1 of 3	3
ZNF503-AS1	ENST00000531808.5	n.456-5139C>T		intron_variant	Intron 2 of 2	4

Frequencies

GnomAD3 genomes AF: 0.500 AC: 75997 AN: 151880 Hom.: 20352 Cov.: 32

Gnomad AFR AF: 0.305

Gnomad AMI AF: 0.644

Gnomad AMR AF: 0.468

Gnomad ASJ AF: 0.482

Gnomad EAS AF: 0.469

Gnomad SAS AF: 0.633

Gnomad FIN AF: 0.636

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.596

Gnomad OTH AF: 0.535

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

GnomAD4 genome AF: 0.500 AC: 76024 AN: 151998 Hom.: 20347 Cov.: 32 AF XY: 0.506 AC XY: 37568 AN XY: 74284

African (AFR) AF: 0.305 AC: 12638 AN: 41454

American (AMR) AF: 0.468 AC: 7147 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.482 AC: 1673 AN: 3468

East Asian (EAS) AF: 0.469 AC: 2413 AN: 5142

South Asian (SAS) AF: 0.632 AC: 3046 AN: 4822

European-Finnish (FIN) AF: 0.636 AC: 6712 AN: 10556

Middle Eastern (MID) AF: 0.585 AC: 172 AN: 294

European-Non Finnish (NFE) AF: 0.596 AC: 40514 AN: 67960

Other (OTH) AF: 0.532 AC: 1122 AN: 2108

Alfa AF: 0.563 Hom.: 103729

Bravo AF: 0.472

Asia WGS AF: 0.520 AC: 1806 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.0
DANN	Benign	0.56
PhyloP100		0.076

Splicing

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

Other links and lift over

dbSNP: rs1259590; hg19: chr10-77128000;