Variant chr19-37565268-C-G 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_016536.5(ZNF571):c.1160G>C(p.Gly387Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000782 in 1,611,300 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000086 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000077 ( 0 hom. )

Consequence

ZNF571
NM_016536.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.77

Variant links:

Genes affected

ZNF571 (HGNC:25000): (zinc finger protein 571) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF571 links:

ZNF571-AS1 (HGNC:44324): (ZNF571 antisense RNA 1)

ZNF571-AS1 links:

ZNF540 (HGNC:25331): (zinc finger protein 540) Enables translation repressor activity, mRNA regulatory element binding. Involved in negative regulation of transcription, DNA-templated and negative regulation of translation. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ZNF540 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=0.03616801).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF571	NM_016536.5 linkuse as main transcript	c.1160G>C	p.Gly387Ala	missense_variant	4/4	ENST00000451802.7
ZNF571-AS1	NR_038248.1 linkuse as main transcript	n.338-763C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF571	ENST00000451802.7 linkuse as main transcript	c.1160G>C	p.Gly387Ala	missense_variant	4/4	1	NM_016536.5	P1
ZNF571-AS1	ENST00000585578.5 linkuse as main transcript	n.210-763C>G		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes

AF:

0.0000855

AC:

AN:

152022

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00375

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000153

AC:

AN:

247842

Hom.:

AF XY:

0.000134

AC XY:

AN XY:

134072

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00317

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000356

Gnomad OTH exome

AF:

0.000501

GnomAD4 exome

AF:

0.0000774

AC:

113

AN:

1459278

Hom.:

Cov.:

AF XY:

0.0000785

AC XY:

AN XY:

725888

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00297

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000135

Gnomad4 OTH exome

AF:

0.000332

GnomAD4 genome

AF:

0.0000855

AC:

AN:

152022

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74240

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00375

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000383

Hom.:

Bravo

AF:

0.000102

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000659

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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

Dec 06, 2021

The c.1160G>C (p.G387A) alteration is located in exon 4 (coding exon 3) of the ZNF571 gene. This alteration results from a G to C substitution at nucleotide position 1160, causing the glycine (G) at amino acid position 387 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

Uncertain

0.43

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.014

T;T;T;T

Eigen

Uncertain

0.28

Eigen_PC

Benign

0.21

FATHMM_MKL

Benign

0.0050

LIST_S2

Benign

0.66

T;.;.;.

M_CAP

Benign

0.015

MetaRNN

Benign

0.036

T;T;T;T

MetaSVM

Benign

-0.80

MutationAssessor

Uncertain

2.2

M;M;M;M

MutationTaster

Benign

1.0

D;D;D;D;D;D

PrimateAI

Benign

0.38

PROVEAN

Pathogenic

-5.4

D;.;D;D

REVEL

Benign

0.17

Sift

Uncertain

0.017

D;.;D;D

Sift4G

Uncertain

0.0030

D;D;D;D

Polyphen

0.93

P;P;P;P

Vest4

0.26

MVP

0.37

MPC

0.23

ClinPred

0.41

GERP RS

3.6

Varity_R

0.21

gMVP

0.012

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