19-36892308-A-C

Position:

• chr19-36892308-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The ENST00000391711.8(ZNF829):​c.483T>G​(p.Cys161Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF829 ENST00000391711.8 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.344

Genes affected

ZNF829 (HGNC:34032): (zinc finger protein 829) 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 located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF345 (HGNC:16367): (zinc finger protein 345) Enables sequence-specific double-stranded 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 Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.881

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF829	NM_001037232.4	c.483T>G	p.Cys161Trp	missense_variant	6/6	ENST00000391711.8	NP_001032309.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF829	ENST00000391711.8	c.483T>G	p.Cys161Trp	missense_variant	6/6	1	NM_001037232.4	ENSP00000429266	P2

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 specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 02, 2021

The c.726T>G (p.C242W) alteration is located in exon 6 (coding exon 6) of the ZNF829 gene. This alteration results from a T to G substitution at nucleotide position 726, causing the cysteine (C) at amino acid position 242 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.47
BayesDel_addAF	Pathogenic	0.29	D
BayesDel_noAF	Pathogenic	0.19
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.36	.;T
Eigen	Benign	0.083
Eigen_PC	Benign	-0.19
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.43	T;T
M_CAP	Pathogenic	0.36	D
MetaRNN	Pathogenic	0.88	D;D
MetaSVM	Pathogenic	0.80	D
MutationAssessor	Pathogenic	4.4	.;H
MutationTaster	Benign	0.99	D;D;D
PrimateAI	Uncertain	0.52	T
PROVEAN	Pathogenic	-11	D;D
REVEL	Pathogenic	0.69
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	.;D
Vest4		0.44
MutPred		0.76		.;Gain of MoRF binding (P = 0.0165);
MVP		0.81
MPC		0.65
ClinPred		1.0	D
GERP RS		-1.1
Varity_R		0.69
gMVP		0.18

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: chr19-37383210;