chr19-44129800-G-A

Variant names:

• chr19-44129800-G-A
• rs10406335
• NM_013362.4:c.236-1050G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013362.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF225	NM_013362.4	MANE Select	c.236-1050G>A		intron	N/A	NP_037494.2	Q9UK10
	ZNF225	NM_001321685.2		c.236-1050G>A		intron	N/A	NP_001308614.1	Q9UK10

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF225	ENST00000262894.11	TSL:1 MANE Select	c.236-1050G>A		intron	N/A	ENSP00000262894.5	Q9UK10
	ZNF225	ENST00000590612.1	TSL:1	c.236-1050G>A		intron	N/A	ENSP00000468686.1	Q9UK10
	ZNF225	ENST00000860840.1		c.236-1050G>A		intron	N/A	ENSP00000530899.1

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.750 AC: 15 AN: 20

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.674 AC: 27923 AN: 41438

American (AMR) AF: 0.628 AC: 9596 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.863 AC: 2994 AN: 3470

East Asian (EAS) AF: 0.524 AC: 2703 AN: 5158

South Asian (SAS) AF: 0.761 AC: 3658 AN: 4804

European-Finnish (FIN) AF: 0.806 AC: 8528 AN: 10584

Middle Eastern (MID) AF: 0.866 AC: 253 AN: 292

European-Non Finnish (NFE) AF: 0.878 AC: 59694 AN: 68006

Other (OTH) AF: 0.796 AC: 1677 AN: 2108

Alfa AF: 0.842 Hom.: 91188

Bravo AF: 0.755

Asia WGS AF: 0.630 AC: 2194 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	5.5
DANN	Benign	0.62
PhyloP100		0.41
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: rs10406335; hg19: chr19-44633953;