rs487939

Variant names:

• chrX-130241196-C-A
• rs487939
• NM_017666.5:c.382-1503G>T

Variant summary

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

The NM_017666.5(ZNF280C):​c.382-1503G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.503 in 110,040 control chromosomes in the GnomAD database, including 10,816 homozygotes. There are 16,065 hemizygotes in GnomAD. 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 (10816 hom., 16065 hem., cov: 22)
• Consequence: ZNF280C NM_017666.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.124
• Publications: 1 publications found

Genes affected

ZNF280C (HGNC:25955): (zinc finger protein 280C) This gene encodes a member of the zinc finger domain-containing protein family. This family member contains multiple Cys2-His2(C2H2)-type zinc finger domains, the most common type of zinc finger domain that self-folds to form a beta-beta-alpha structure that binds a zinc ion. [provided by RefSeq, Aug 2011]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.713 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF280C	NM_017666.5	c.382-1503G>T		intron_variant	Intron 5 of 18	ENST00000370978.9	NP_060136.1
ZNF280C	XM_006724765.4	c.382-1503G>T		intron_variant	Intron 5 of 17		XP_006724828.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF280C	ENST00000370978.9	c.382-1503G>T		intron_variant	Intron 5 of 18	1	NM_017666.5	ENSP00000360017.4
ZNF280C	ENST00000447817.1	c.382-1503G>T		intron_variant	Intron 5 of 13	1		ENSP00000408521.1

Frequencies

GnomAD3 genomes AF: 0.503 AC: 55341 AN: 109990 Hom.: 10810 Cov.: 22

Gnomad AFR AF: 0.720

Gnomad AMI AF: 0.664

Gnomad AMR AF: 0.462

Gnomad ASJ AF: 0.497

Gnomad EAS AF: 0.338

Gnomad SAS AF: 0.494

Gnomad FIN AF: 0.433

Gnomad MID AF: 0.479

Gnomad NFE AF: 0.404

Gnomad OTH AF: 0.494

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

GnomAD4 genome AF: 0.503 AC: 55395 AN: 110040 Hom.: 10816 Cov.: 22 AF XY: 0.497 AC XY: 16065 AN XY: 32334

African (AFR) AF: 0.721 AC: 21871 AN: 30350

American (AMR) AF: 0.462 AC: 4743 AN: 10256

Ashkenazi Jewish (ASJ) AF: 0.497 AC: 1302 AN: 2618

East Asian (EAS) AF: 0.339 AC: 1185 AN: 3500

South Asian (SAS) AF: 0.494 AC: 1279 AN: 2587

European-Finnish (FIN) AF: 0.433 AC: 2465 AN: 5696

Middle Eastern (MID) AF: 0.484 AC: 103 AN: 213

European-Non Finnish (NFE) AF: 0.404 AC: 21264 AN: 52658

Other (OTH) AF: 0.495 AC: 740 AN: 1495

Alfa AF: 0.458 Hom.: 3220

Bravo AF: 0.515

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.2
DANN	Benign	0.71
PhyloP100		0.12
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: rs487939; hg19: chrX-129375170;