Variant 19-7083160-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_024341.3(ZNF557):c.709G>A(p.Glu237Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000582 in 1,613,930 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000062 ( 0 hom. )

Consequence

ZNF557
NM_024341.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.47

Variant links:

Genes affected

ZNF557 (HGNC:28632): (zinc finger protein 557) 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]

ZNF557 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.03289911).

BP6

Variant 19-7083160-G-A is Benign according to our data. Variant chr19-7083160-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3196685.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF557	NM_024341.3 linkuse as main transcript	c.709G>A	p.Glu237Lys	missense_variant	8/8	ENST00000252840.11	NP_077317.2	Q8N988-2
ZNF557	NM_001044387.2 linkuse as main transcript	c.709G>A	p.Glu237Lys	missense_variant	8/8		NP_001037852.1	Q8N988-2
ZNF557	NM_001044388.2 linkuse as main transcript	c.688G>A	p.Glu230Lys	missense_variant	8/8		NP_001037853.1	Q8N988-1
ZNF557	XM_047439432.1 linkuse as main transcript	c.688G>A	p.Glu230Lys	missense_variant	8/8		XP_047295388.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF557	ENST00000252840.11 linkuse as main transcript	c.709G>A	p.Glu237Lys	missense_variant	8/8	1	NM_024341.3	ENSP00000252840.5		Q8N988-2
ZNF557	ENST00000414706.2 linkuse as main transcript	c.688G>A	p.Glu230Lys	missense_variant	8/8	2		ENSP00000404065.2		Q8N988-1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152062

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000120

AC:

AN:

250390

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135766

show subpopulations

Gnomad AFR exome

AF:

0.0000642

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000622

AC:

AN:

1461868

Hom.:

Cov.:

AF XY:

0.0000660

AC XY:

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000773

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152062

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74286

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000658

Hom.:

Bravo

AF:

0.0000264

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.000229

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000247

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 14, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.78

CADD

Benign

9.8

DANN

Benign

0.56

DEOGEN2

Benign

0.050

.;T

Eigen

Benign

-2.0

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.0

LIST_S2

Benign

0.18

T;T

M_CAP

Benign

0.00090

MetaRNN

Benign

0.033

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-1.4

.;N

PrimateAI

Benign

0.33

PROVEAN

Benign

-2.1

N;.

REVEL

Benign

0.017

Sift

Benign

0.11

T;.

Sift4G

Benign

0.26

T;T

Polyphen

0.0

B;B

Vest4

0.096

MVP

0.13

MPC

0.074

ClinPred

0.018

GERP RS

-2.4

Varity_R

0.079

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