19-21508995-C-T

Variant names:

• chr19-21508995-C-T
• rs1984771
• NM_001001415.4:c.3+3221C>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+3221C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 151,744 control chromosomes in the GnomAD database, including 2,997 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 0.20 (2997 hom., cov: 31)
• Consequence: ZNF429 NM_001001415.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.377
• Publications: 12 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.218 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+3221C>T		intron	N/A	NP_001001415.2	Q86V71
	ZNF429	NM_001346912.2		c.16+2915C>T		intron	N/A	NP_001333841.1
	ZNF429	NM_001346913.2		c.-94+2915C>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+3221C>T		intron	N/A	ENSP00000351280.3	Q86V71
	ZNF429	ENST00000597078.5	TSL:1	c.3+3221C>T		intron	N/A	ENSP00000470300.1	M0QZ47
	ZNF429	ENST00000967842.1		c.3+3221C>T		intron	N/A	ENSP00000637901.1

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29754 AN: 151628 Hom.: 2988 Cov.: 31

Gnomad AFR AF: 0.221

Gnomad AMI AF: 0.191

Gnomad AMR AF: 0.179

Gnomad ASJ AF: 0.243

Gnomad EAS AF: 0.0768

Gnomad SAS AF: 0.182

Gnomad FIN AF: 0.192

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.193

Gnomad OTH AF: 0.196

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

GnomAD4 genome AF: 0.196 AC: 29791 AN: 151744 Hom.: 2997 Cov.: 31 AF XY: 0.196 AC XY: 14555 AN XY: 74120

African (AFR) AF: 0.222 AC: 9159 AN: 41342

American (AMR) AF: 0.179 AC: 2727 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.243 AC: 842 AN: 3466

East Asian (EAS) AF: 0.0769 AC: 397 AN: 5160

South Asian (SAS) AF: 0.181 AC: 868 AN: 4802

European-Finnish (FIN) AF: 0.192 AC: 2012 AN: 10494

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.193 AC: 13141 AN: 67942

Other (OTH) AF: 0.193 AC: 407 AN: 2106

Alfa AF: 0.194 Hom.: 8060

Bravo AF: 0.198

Asia WGS AF: 0.132 AC: 458 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.0
DANN	Benign	0.70
PhyloP100		0.38
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: rs1984771; hg19: chr19-21691797;