rs10406335

chr19-44129800-G-A

Variant summary

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

The NM_013362.4(ZNF225):c.236-1050G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.774 in 152,064 control chromosomes in the GnomAD database, including 46,727 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 0.77 (46722 hom., cov: 31)
  • Exomes 𝑓: 0.75 (5 hom.)
• Consequence: ZNF225 NM_013362.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.409

Genes affected

ZNF225 (HGNC:13018): (zinc finger protein 225) Predicted to enable DNA-binding transcription activator activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [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=-1.02).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.872 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF225	NM_013362.4	c.236-1050G>A		intron_variant		ENST00000262894.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF225	ENST00000262894.11	c.236-1050G>A		intron_variant		1	NM_013362.4	P1

Frequencies

GnomAD3 genomes AF: 0.775 AC: 117698 AN: 151926 Hom.: 46702 Cov.: 31

Gnomad AFR AF: 0.674

Gnomad AMI AF: 0.802

Gnomad AMR AF: 0.629

Gnomad ASJ AF: 0.863

Gnomad EAS AF: 0.524

Gnomad SAS AF: 0.760

Gnomad FIN AF: 0.806

Gnomad MID AF: 0.873

Gnomad NFE AF: 0.878

Gnomad OTH AF: 0.799

GnomAD4 exome AF: 0.750 AC: 15 AN: 20 Hom.: 5 Cov.: 0 AF XY: 0.750 AC XY: 9 AN XY: 12

Gnomad4 NFE exome AF: 0.750

GnomAD4 genome AF: 0.774 AC: 117756 AN: 152044 Hom.: 46722 Cov.: 31 AF XY: 0.766 AC XY: 56935 AN XY: 74334

Gnomad4 AFR AF: 0.674

Gnomad4 AMR AF: 0.628

Gnomad4 ASJ AF: 0.863

Gnomad4 EAS AF: 0.524

Gnomad4 SAS AF: 0.761

Gnomad4 FIN AF: 0.806

Gnomad4 NFE AF: 0.878

Gnomad4 OTH AF: 0.796

Alfa AF: 0.852 Hom.: 73138

Bravo AF: 0.755

Asia WGS AF: 0.630 AC: 2194 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	5.5
Dann	Benign	0.62

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: rs10406335; hg19: chr19-44633953;