19-11867692-A-C

Variant names:

• chr19-11867692-A-C
• NM_001348719.2:c.638A>C

Variant summary

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

The NM_001348719.2(ZNF439):​c.638A>C​(p.His213Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF439 NM_001348719.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.08

Genes affected

ZNF439 (HGNC:20873): (zinc finger protein 439) 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]

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 rank	MANE	Protein	UniProt
ZNF439	NM_001348719.2	c.638A>C	p.His213Pro	missense_variant	Exon 4 of 4	ENST00000682736.1	NP_001335648.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF439	ENST00000682736.1	c.638A>C	p.His213Pro	missense_variant	Exon 4 of 4		NM_001348719.2	ENSP00000506930.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 07, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.623A>C (p.H208P) alteration is located in exon 3 (coding exon 3) of the ZNF439 gene. This alteration results from a A to C substitution at nucleotide position 623, causing the histidine (H) at amino acid position 208 to be replaced by a proline (P). 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	Benign	0.26
BayesDel_addAF	Uncertain	0.040	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	18
DANN	Benign	0.83
DEOGEN2	Benign	0.13	.;T
Eigen	Benign	-0.024
Eigen_PC	Benign	-0.38
FATHMM_MKL	Benign	0.073	N
LIST_S2	Benign	0.55	T;T
M_CAP	Benign	0.0021	T
MetaRNN	Uncertain	0.66	D;D
MetaSVM	Benign	-0.54	T
MutationAssessor	Pathogenic	4.1	.;H
PrimateAI	Benign	0.43	T
PROVEAN	Pathogenic	-9.5	D;D
REVEL	Benign	0.16
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	.;D
Vest4		0.34
MutPred		0.70		.;Gain of relative solvent accessibility (P = 0.1259);
MVP		0.88
MPC		0.41
ClinPred		0.89	D
GERP RS		0.64
Varity_R		0.32
gMVP		0.080

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: chr19-11978507;