19-36891630-C-A

Position:

• chr19-36891630-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001037232.4(ZNF829):​c.1161G>T​(p.Lys387Asn) 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 benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF829 NM_001037232.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.90

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]

ENSG00000291239 (HGNC:):

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24050361).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF829	NM_001037232.4	c.1161G>T	p.Lys387Asn	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.1161G>T	p.Lys387Asn	missense_variant	6/6	1	NM_001037232.4	ENSP00000429266.1
ENSG00000291239	ENST00000706165.1	c.-423-1188C>A		intron_variant				ENSP00000516244.1

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

Mar 04, 2024

The c.1404G>T (p.K468N) alteration is located in exon 6 (coding exon 6) of the ZNF829 gene. This alteration results from a G to T substitution at nucleotide position 1404, causing the lysine (K) at amino acid position 468 to be replaced by an asparagine (N). 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	Pathogenic	0.91
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	17
DANN	Uncertain	1.0
DEOGEN2	Benign	0.22	.;T
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.29
FATHMM_MKL	Benign	0.048	N
LIST_S2	Benign	0.31	T;T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.24	T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Pathogenic	3.2	.;M
PrimateAI	Benign	0.45	T
PROVEAN	Pathogenic	-4.8	.;D
REVEL	Benign	0.14
Sift	Uncertain	0.0080	.;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		0.71	.;P
Vest4		0.34
MutPred		0.56		.;Loss of methylation at K387 (P = 0.0031);
MVP		0.19
MPC		0.33
ClinPred		0.84	D
GERP RS		2.0
Varity_R		0.33
gMVP		0.024

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

LitVar

Other links and lift over

dbSNP: rs990493512; hg19: chr19-37382532;