Variant 19-51964883-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_021632.4(ZNF350):c.1570G>A(p.Val524Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000786 in 1,612,358 control chromosomes in the GnomAD database, including 5 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 Likely benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0011 ( 2 hom., cov: 33)

Exomes 𝑓: 0.00075 ( 3 hom. )

Consequence

ZNF350
NM_021632.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.72

Variant links:

Genes affected

ZNF350 (HGNC:16656): (zinc finger protein 350) Enables DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II intronic transcription regulatory region sequence-specific DNA binding activity. Involved in negative regulation of transcription by RNA polymerase II. Located in nuclear body. Part of transcription repressor complex. [provided by Alliance of Genome Resources, Apr 2022]

ZNF350 links:

ZNF350-AS1 (HGNC:48598): (ZNF350 antisense RNA 1)

ZNF350-AS1 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=0.0044547915).

BP6

Variant 19-51964883-C-T is Benign according to our data. Variant chr19-51964883-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2650380.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF350	NM_021632.4 linkuse as main transcript	c.1570G>A	p.Val524Ile	missense_variant	5/5	ENST00000243644.9
ZNF350-AS1	NR_103847.1 linkuse as main transcript	n.103-11508C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF350	ENST00000243644.9 linkuse as main transcript	c.1570G>A	p.Val524Ile	missense_variant	5/5	1	NM_021632.4	P1
ZNF350-AS1	ENST00000595010.4 linkuse as main transcript	n.121-11508C>T		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes

AF:

0.00114

AC:

173

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.0844

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00119

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000675

AC:

169

AN:

250436

Hom.:

AF XY:

0.000724

AC XY:

AN XY:

135310

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.000638

Gnomad ASJ exome

AF:

0.00140

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000655

Gnomad FIN exome

AF:

0.0000463

Gnomad NFE exome

AF:

0.00111

Gnomad OTH exome

AF:

0.000328

GnomAD4 exome

AF:

0.000750

AC:

1095

AN:

1460040

Hom.:

Cov.:

AF XY:

0.000726

AC XY:

527

AN XY:

725934

show subpopulations

Gnomad4 AFR exome

AF:

0.000269

Gnomad4 AMR exome

AF:

0.000717

Gnomad4 ASJ exome

AF:

0.00188

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000696

Gnomad4 FIN exome

AF:

0.000169

Gnomad4 NFE exome

AF:

0.000860

Gnomad4 OTH exome

AF:

0.000564

GnomAD4 genome

AF:

0.00114

AC:

173

AN:

152318

Hom.:

Cov.:

AF XY:

0.00107

AC XY:

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.000144

Gnomad4 AMR

AF:

0.000261

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00119

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00104

Hom.:

Bravo

AF:

0.00126

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00116

AC:

ExAC

AF:

0.000642

AC:

EpiCase

AF:

0.000491

EpiControl

AF:

0.00136

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

May 01, 2022

ZNF350: BP4 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.80

CADD

Benign

7.1

DANN

Benign

0.28

DEOGEN2

Benign

0.027

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.0091

LIST_S2

Benign

0.65

M_CAP

Benign

0.0013

MetaRNN

Benign

0.0045

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.72

MutationTaster

Benign

1.0

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.20

REVEL

Benign

0.035

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.053

Vest4

0.054

MVP

0.22

MPC

0.17

ClinPred

0.014

GERP RS

-1.8

Varity_R

0.051

gMVP

0.075

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