Genetic Variant ZNF350:p.Val524Ile (chr19-51964883-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -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. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

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

Publications

5 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 2650380.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021632.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF350	NM_021632.4	MANE Select	c.1570G>A	p.Val524Ile	missense	Exon 5 of 5	NP_067645.3
	ZNF350-AS1	NR_103847.1		n.103-11508C>T		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZNF350	ENST00000243644.9	TSL:1 MANE Select	c.1570G>A	p.Val524Ile	missense	Exon 5 of 5	ENSP00000243644.3	Q9GZX5
ZNF350-AS1	ENST00000595010.5	TSL:1	n.125-11508C>T		intron	N/A
ZNF350	ENST00000853589.1		c.1639G>A	p.Val547Ile	missense	Exon 6 of 6	ENSP00000523648.1

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

GnomAD2 exomes

AF:

0.000675

AC:

169

AN:

250436

AF XY:

0.000724

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 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

African (AFR)

AF:

0.000269

AC:

AN:

33466

American (AMR)

AF:

0.000717

AC:

AN:

44638

Ashkenazi Jewish (ASJ)

AF:

0.00188

AC:

AN:

26086

East Asian (EAS)

AF:

0.00

AC:

AN:

39630

South Asian (SAS)

AF:

0.0000696

AC:

AN:

86170

European-Finnish (FIN)

AF:

0.000169

AC:

AN:

53402

Middle Eastern (MID)

AF:

0.000174

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.000860

AC:

955

AN:

1110584

Other (OTH)

AF:

0.000564

AC:

AN:

60302

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

116

173

231

289

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

102

136

170

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00114

AC:

173

AN:

152318

Hom.:

Cov.:

AF XY:

0.00107

AC XY:

AN XY:

74484

show subpopulations

African (AFR)

AF:

0.000144

AC:

AN:

41572

American (AMR)

AF:

0.000261

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00144

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00119

AC:

AN:

68026

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000999

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

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.80

CADD

Benign

7.1

(source)

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

PhyloP100

-3.7

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

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over