X-130215321-T-G

Variant names:

• chrX-130215321-T-G
• rs209238
• NM_017666.5:c.1851A>C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_017666.5(ZNF280C):​c.1851A>C​(p.Gly617Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.426 in 1,189,339 control chromosomes in the GnomAD database, including 75,830 homozygotes. There are 163,095 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 0.49 (10194 hom., 15409 hem., cov: 22)
  • Exomes 𝑓: 0.42 (65636 hom. 147686 hem.)
• Consequence: ZNF280C NM_017666.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.39

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

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP7: Synonymous conserved (PhyloP=1.39 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.674 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF280C	NM_017666.5	c.1851A>C	p.Gly617Gly	synonymous_variant	Exon 15 of 19	ENST00000370978.9	NP_060136.1
ZNF280C	XM_006724765.4	c.1704A>C	p.Gly568Gly	synonymous_variant	Exon 14 of 18		XP_006724828.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF280C	ENST00000370978.9	c.1851A>C	p.Gly617Gly	synonymous_variant	Exon 15 of 19	1	NM_017666.5	ENSP00000360017.4
ZNF280C	ENST00000447817.1	c.1704A>C	p.Gly568Gly	synonymous_variant	Exon 14 of 14	1		ENSP00000408521.1

Frequencies

GnomAD3 genomes AF: 0.492 AC: 53816 AN: 109484 Hom.: 10190 Cov.: 22 AF XY: 0.483 AC XY: 15370 AN XY: 31814

Gnomad AFR AF: 0.682

Gnomad AMI AF: 0.660

Gnomad AMR AF: 0.461

Gnomad ASJ AF: 0.499

Gnomad EAS AF: 0.333

Gnomad SAS AF: 0.496

Gnomad FIN AF: 0.429

Gnomad MID AF: 0.466

Gnomad NFE AF: 0.404

Gnomad OTH AF: 0.490

GnomAD3 exomes AF: 0.442 AC: 72809 AN: 164568 Hom.: 11462 AF XY: 0.438 AC XY: 23344 AN XY: 53300

Gnomad AFR exome AF: 0.691

Gnomad AMR exome AF: 0.452

Gnomad ASJ exome AF: 0.481

Gnomad EAS exome AF: 0.339

Gnomad SAS exome AF: 0.496

Gnomad FIN exome AF: 0.426

Gnomad NFE exome AF: 0.406

Gnomad OTH exome AF: 0.440

GnomAD4 exome AF: 0.420 AC: 453341 AN: 1079808 Hom.: 65636 Cov.: 28 AF XY: 0.422 AC XY: 147686 AN XY: 350174

Gnomad4 AFR exome AF: 0.702

Gnomad4 AMR exome AF: 0.456

Gnomad4 ASJ exome AF: 0.478

Gnomad4 EAS exome AF: 0.342

Gnomad4 SAS exome AF: 0.493

Gnomad4 FIN exome AF: 0.422

Gnomad4 NFE exome AF: 0.405

Gnomad4 OTH exome AF: 0.449

GnomAD4 genome AF: 0.492 AC: 53852 AN: 109531 Hom.: 10194 Cov.: 22 AF XY: 0.483 AC XY: 15409 AN XY: 31871

Gnomad4 AFR AF: 0.682

Gnomad4 AMR AF: 0.461

Gnomad4 ASJ AF: 0.499

Gnomad4 EAS AF: 0.334

Gnomad4 SAS AF: 0.496

Gnomad4 FIN AF: 0.429

Gnomad4 NFE AF: 0.404

Gnomad4 OTH AF: 0.489

Alfa AF: 0.423 Hom.: 12341

Bravo AF: 0.503

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	4.2
DANN	Benign	0.74

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs209238; hg19: chrX-129349295; COSMIC: COSV100921178;