19-52016024-A-G

Position:

• chr19-52016024-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_025040.4(ZNF614):​c.1574T>C​(p.Val525Ala) 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. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF614 NM_025040.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.73

Genes affected

ZNF614 (HGNC:24722): (zinc finger protein 614) 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]

LOC124904755 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06377792).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF614	NM_025040.4	c.1574T>C	p.Val525Ala	missense_variant	5/5	ENST00000270649.11	NP_079316.2
LOC124904755	XR_007067321.1	n.183-5227A>G		intron_variant
LOC124904755	XR_007067322.1	n.183-5227A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF614	ENST00000270649.11	c.1574T>C	p.Val525Ala	missense_variant	5/5	1	NM_025040.4	ENSP00000270649.5
ZNF614	ENST00000356322.10	c.481+1093T>C		intron_variant		1		ENSP00000348674.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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 05, 2024

The c.1574T>C (p.V525A) alteration is located in exon 5 (coding exon 4) of the ZNF614 gene. This alteration results from a T to C substitution at nucleotide position 1574, causing the valine (V) at amino acid position 525 to be replaced by an alanine (A). 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	0.69
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	6.7
DANN	Benign	0.51
DEOGEN2	Benign	0.0021	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0077	N
LIST_S2	Benign	0.068	T
M_CAP	Benign	0.0014	T
MetaRNN	Benign	0.064	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-0.55	N
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	0.96	N
REVEL	Benign	0.020
Sift	Benign	0.84	T
Sift4G	Benign	0.92	T
Polyphen		0.32	B
Vest4		0.086
MutPred		0.25		Loss of stability (P = 0.0293);
MVP		0.17
MPC		0.41
ClinPred		0.079	T
GERP RS		-0.18
Varity_R		0.028
gMVP		0.045

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: chr19-52519277;