19-19711708-G-C

Variant names:

• chr19-19711708-G-C
• NM_021030.3:c.1573C>G

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_021030.3(ZNF14):​c.1573C>G​(p.His525Asp) variant causes a missense change. 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: 33)
• Consequence: ZNF14 NM_021030.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.14

Genes affected

ZNF14 (HGNC:12924): (zinc finger protein 14) The protein encoded by this gene contains a zinc finger and a Kruppel-associated box (KRAB) domain. KRAB domain is known to be involved in the transcriptional repression of a number of zinc finger proteins. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.954

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF14	NM_021030.3	c.1573C>G	p.His525Asp	missense_variant	Exon 4 of 4	ENST00000344099.4	NP_066358.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF14	ENST00000344099.4	c.1573C>G	p.His525Asp	missense_variant	Exon 4 of 4	1	NM_021030.3	ENSP00000340514.2

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

Aug 28, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1573C>G (p.H525D) alteration is located in exon 4 (coding exon 4) of the ZNF14 gene. This alteration results from a C to G substitution at nucleotide position 1573, causing the histidine (H) at amino acid position 525 to be replaced by an aspartic acid (D). 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	0.87
BayesDel_addAF	Uncertain	0.015	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.45	T
Eigen	Uncertain	0.41
Eigen_PC	Benign	0.13
FATHMM_MKL	Benign	0.077	N
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.0027	T
MetaRNN	Pathogenic	0.95	D
MetaSVM	Uncertain	0.14	D
MutationAssessor	Pathogenic	3.8	H
PrimateAI	Uncertain	0.49	T
PROVEAN	Pathogenic	-8.1	D
REVEL	Benign	0.25
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.32
MutPred		0.90		Loss of methylation at K523 (P = 0.0537);
MVP		0.83
MPC		0.36
ClinPred		1.0	D
GERP RS		1.8
Varity_R		0.48
gMVP		0.071

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: chr19-19822517;