19-9757722-C-T

Position:

• chr19-9757722-C-T

Variant summary

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

The NM_001077624.3(ZNF846):​c.1355G>A​(p.Cys452Tyr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF846 NM_001077624.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.70

Genes affected

ZNF846 (HGNC:27260): (zinc finger protein 846) Predicted to enable DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Predicted to be involved in negative regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF846 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF846	NM_001077624.3	c.1355G>A	p.Cys452Tyr	missense_variant	6/6	ENST00000397902.7	NP_001071092.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF846	ENST00000397902.7	c.1355G>A	p.Cys452Tyr	missense_variant	6/6	1	NM_001077624.3	ENSP00000380999.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 33

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

Jun 07, 2023

The c.1355G>A (p.C452Y) alteration is located in exon 6 (coding exon 5) of the ZNF846 gene. This alteration results from a G to A substitution at nucleotide position 1355, causing the cysteine (C) at amino acid position 452 to be replaced by a tyrosine (Y). 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	0.78
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.080
CADD	Benign	19
DANN	Benign	0.96
DEOGEN2	Benign	0.26	T
Eigen	Uncertain	0.25
Eigen_PC	Benign	-0.0074
FATHMM_MKL	Benign	0.059	N
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.013	T
MetaRNN	Uncertain	0.74	D
MetaSVM	Uncertain	-0.052	T
MutationAssessor	Pathogenic	3.8	H
PrimateAI	Uncertain	0.64	T
PROVEAN	Pathogenic	-11	D
REVEL	Uncertain	0.45
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.52
MutPred		0.71		Loss of methylation at K453 (P = 0.035);
MVP		0.38
MPC		0.074
ClinPred		1.0	D
GERP RS		2.0
Varity_R		0.93
gMVP		0.074

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: chr19-9868398;