4-145849389-TG-T

Variant summary

Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1 PM2

The NM_001306215.2(ZNF827):c.2153del(p.Pro718GlnfsTer12) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF827 NM_001306215.2 frameshift
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.13

Genes affected

ZNF827 (HGNC:27193): (zinc finger protein 827) Predicted to enable DNA binding activity and metal ion binding activity. Predicted to be involved in positive 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 Pathogenic. Variant got 10 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF827	NM_001306215.2	c.2153del	p.Pro718GlnfsTer12	frameshift_variant	6/15	ENST00000508784.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF827	ENST00000508784.6	c.2153del	p.Pro718GlnfsTer12	frameshift_variant	6/15	1	NM_001306215.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 07, 2021

The ZNF827 c.2153delC (p.Pro718GlnfsTer12) variant is a frameshift variant that is expected to result in an absent or prematurely truncated protein product. A literature search was conducted for the gene, cDNA change, and amino acid change. No publications were identified through this search. This variant is absent from version 2.1.1 and version 3.1.1 of the Genome Aggregation Database despite its location in a region of good sequencing coverage, which suggests the variant is rare. Based on the available evidence, the p.Pro718GlnfsTer12 variant is classified as a variant of uncertain significance. -

Computational scores

Source: dbNSFP v4.3

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-146770541;