19-21516423-C-T

Variant names:

• chr19-21516423-C-T
• rs2650825
• NM_001001415.4:c.3+10649C>T

Variant summary

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

The NM_001001415.4(ZNF429):​c.3+10649C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.806 in 152,084 control chromosomes in the GnomAD database, including 50,103 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 0.81 (50103 hom., cov: 32)
• Consequence: ZNF429 NM_001001415.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.26
• Publications: 8 publications found

Genes affected

ZNF429 (HGNC:20817): (zinc finger protein 429) Predicted to enable DNA-binding transcription factor 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 (AFR) allele frequency at 95% confidence interval = 0.937 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001001415.4. 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
	ZNF429	NM_001001415.4	MANE Select	c.3+10649C>T		intron	N/A	NP_001001415.2	Q86V71
	ZNF429	NM_001346912.2		c.16+10343C>T		intron	N/A	NP_001333841.1
	ZNF429	NM_001346913.2		c.-94+10343C>T		intron	N/A	NP_001333842.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF429	ENST00000358491.9	TSL:3 MANE Select	c.3+10649C>T		intron	N/A	ENSP00000351280.3	Q86V71
	ZNF429	ENST00000597078.5	TSL:1	c.3+10649C>T		intron	N/A	ENSP00000470300.1	M0QZ47
	ZNF429	ENST00000967842.1		c.3+10649C>T		intron	N/A	ENSP00000637901.1

Frequencies

GnomAD3 genomes AF: 0.806 AC: 122545 AN: 151966 Hom.: 50063 Cov.: 32

Gnomad AFR AF: 0.944

Gnomad AMI AF: 0.745

Gnomad AMR AF: 0.737

Gnomad ASJ AF: 0.834

Gnomad EAS AF: 0.715

Gnomad SAS AF: 0.809

Gnomad FIN AF: 0.755

Gnomad MID AF: 0.842

Gnomad NFE AF: 0.752

Gnomad OTH AF: 0.798

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

GnomAD4 genome AF: 0.806 AC: 122637 AN: 152084 Hom.: 50103 Cov.: 32 AF XY: 0.805 AC XY: 59835 AN XY: 74312

African (AFR) AF: 0.944 AC: 39211 AN: 41516

American (AMR) AF: 0.737 AC: 11252 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.834 AC: 2894 AN: 3470

East Asian (EAS) AF: 0.715 AC: 3700 AN: 5176

South Asian (SAS) AF: 0.808 AC: 3889 AN: 4814

European-Finnish (FIN) AF: 0.755 AC: 7948 AN: 10530

Middle Eastern (MID) AF: 0.840 AC: 247 AN: 294

European-Non Finnish (NFE) AF: 0.752 AC: 51142 AN: 67990

Other (OTH) AF: 0.793 AC: 1675 AN: 2112

Alfa AF: 0.793 Hom.: 6549

Bravo AF: 0.809

Asia WGS AF: 0.739 AC: 2572 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	0.91
DANN	Benign	0.40
PhyloP100		-1.3
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: rs2650825; hg19: chr19-21699225;