Variant chr9-66917837-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_033160.7(ZNF658):c.271C>T(p.Arg91Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00122 in 1,464,896 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. 7/9 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00097 ( 1 hom., cov: 23)

Exomes 𝑓: 0.0012 ( 14 hom. )

Consequence

ZNF658
NM_033160.7 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.60

Variant links:

Genes affected

ZNF658 (HGNC:25226): (zinc finger protein 658) Enables transcription cis-regulatory region binding activity. Involved in cellular response to zinc ion; negative regulation of transcription, DNA-templated; and ribosome biogenesis. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF658 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.014209479).

BP6

Variant 9-66917837-C-T is Benign according to our data. Variant chr9-66917837-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2364981.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 14 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF658	NM_033160.7 linkuse as main transcript	c.271C>T	p.Arg91Trp	missense_variant	5/5	ENST00000621410.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF658	ENST00000621410.5 linkuse as main transcript	c.271C>T	p.Arg91Trp	missense_variant	5/5	2	NM_033160.7	P1	Q5TYW1-1

Frequencies

GnomAD3 genomes

AF:

0.000960

AC:

125

AN:

130276

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000207

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00136

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000661

Gnomad SAS

AF:

0.00724

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00709

Gnomad NFE

AF:

0.00110

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000831

AC:

AN:

119148

Hom.:

AF XY:

0.000890

AC XY:

AN XY:

65202

show subpopulations

Gnomad AFR exome

AF:

0.000254

Gnomad AMR exome

AF:

0.00103

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000971

Gnomad SAS exome

AF:

0.00238

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000705

Gnomad OTH exome

AF:

0.00189

GnomAD4 exome

AF:

0.00124

AC:

1658

AN:

1334548

Hom.:

Cov.:

AF XY:

0.00148

AC XY:

990

AN XY:

667742

show subpopulations

Gnomad4 AFR exome

AF:

0.000803

Gnomad4 AMR exome

AF:

0.00110

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000155

Gnomad4 SAS exome

AF:

0.00695

Gnomad4 FIN exome

AF:

0.0000194

Gnomad4 NFE exome

AF:

0.000910

Gnomad4 OTH exome

AF:

0.00127

GnomAD4 genome

AF:

0.000974

AC:

127

AN:

130348

Hom.:

Cov.:

AF XY:

0.00104

AC XY:

AN XY:

62604

show subpopulations

Gnomad4 AFR

AF:

0.000207

Gnomad4 AMR

AF:

0.00136

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000663

Gnomad4 SAS

AF:

0.00750

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00110

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00123

Hom.:

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

Jul 16, 2021

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

0.072

BayesDel_noAF

Benign

-0.91

CADD

Benign

9.6

DANN

Benign

0.37

LIST_S2

Benign

0.27

T;T;T;T;.

MetaRNN

Benign

0.014

T;T;T;T;T

Sift4G

Benign

0.069

T;T;T;T;T

Vest4

0.071, 0.070

gMVP

0.052

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