Variant chr19-52015850-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_025040.4(ZNF614):c.1748C>T(p.Pro583Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000143 in 1,608,536 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00015 ( 1 hom. )

Consequence

ZNF614
NM_025040.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.283

Variant links:

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]

ZNF614 links:

LOC124904755 (HGNC:):

LOC124904755 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.05266428).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ZNF614	NM_025040.4 linkuse as main transcript	c.1748C>T	p.Pro583Leu	missense_variant	5/5	ENST00000270649.11
LOC124904755	XR_007067321.1 linkuse as main transcript	n.183-5401G>A		intron_variant, non_coding_transcript_variant
LOC124904755	XR_007067322.1 linkuse as main transcript	n.183-5401G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF614	ENST00000270649.11 linkuse as main transcript	c.1748C>T	p.Pro583Leu	missense_variant	5/5	1	NM_025040.4	P1	Q8N883-1
ZNF614	ENST00000356322.10 linkuse as main transcript	c.481+1267C>T		intron_variant		1			Q8N883-2

Frequencies

GnomAD3 genomes

AF:

0.0000723

AC:

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000125

AC:

AN:

247196

Hom.:

AF XY:

0.000157

AC XY:

AN XY:

133550

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000147

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000168

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000179

Gnomad OTH exome

AF:

0.000166

GnomAD4 exome

AF:

0.000150

AC:

219

AN:

1456350

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

107

AN XY:

724150

show subpopulations

Gnomad4 AFR exome

AF:

0.0000301

Gnomad4 AMR exome

AF:

0.000204

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000936

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000146

Gnomad4 OTH exome

AF:

0.000366

GnomAD4 genome

AF:

0.0000723

AC:

AN:

152186

Hom.:

Cov.:

AF XY:

0.0000807

AC XY:

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000207

Hom.:

Bravo

AF:

0.000132

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000148

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 22, 2021

The c.1748C>T (p.P583L) alteration is located in exon 5 (coding exon 4) of the ZNF614 gene. This alteration results from a C to T substitution at nucleotide position 1748, causing the proline (P) at amino acid position 583 to be replaced by a leucine (L). 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

0.086

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.69

CADD

Benign

2.7

DANN

Benign

0.34

DEOGEN2

Benign

0.0069

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.022

LIST_S2

Benign

0.63

M_CAP

Benign

0.0023

MetaRNN

Benign

0.053

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.0

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.11

REVEL

Benign

0.036

Sift

Benign

0.13

Sift4G

Benign

0.69

Polyphen

0.0

Vest4

0.12

MVP

0.28

MPC

0.13

ClinPred

0.010

GERP RS

-1.3

Varity_R

0.020

gMVP

0.049

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over