dbSNP rs4986771: ZNF350:p.Ser472Pro (chr19-51965039-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_021632.4(ZNF350):c.1414T>C(p.Ser472Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0351 in 1,614,098 control chromosomes in the GnomAD database, including 1,191 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.027 ( 69 hom., cov: 32)

Exomes 𝑓: 0.036 ( 1122 hom. )

Consequence

ZNF350
NM_021632.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.334

Publications

17 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0021763444).

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0267 (4063/152230) while in subpopulation NFE AF = 0.0377 (2565/68024). AF 95% confidence interval is 0.0365. There are 69 homozygotes in GnomAd4. There are 2014 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 69 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF350	NM_021632.4 link	c.1414T>C	p.Ser472Pro	missense_variant	Exon 5 of 5	ENST00000243644.9	NP_067645.3	Q9GZX5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF350	ENST00000243644.9 link	c.1414T>C	p.Ser472Pro	missense_variant	Exon 5 of 5	1	NM_021632.4	ENSP00000243644.3		Q9GZX5

Frequencies

GnomAD3 genomes

AF:

0.0267

AC:

4063

AN:

152112

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00705

Gnomad AMI

AF:

0.0877

Gnomad AMR

AF:

0.0298

Gnomad ASJ

AF:

0.0280

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.0313

Gnomad FIN

AF:

0.0327

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0377

Gnomad OTH

AF:

0.0344

GnomAD2 exomes

AF:

0.0305

AC:

7670

AN:

251214

AF XY:

0.0324

show subpopulations

Gnomad AFR exome

AF:

0.00800

Gnomad AMR exome

AF:

0.0209

Gnomad ASJ exome

AF:

0.0268

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0361

Gnomad NFE exome

AF:

0.0385

Gnomad OTH exome

AF:

0.0297

GnomAD4 exome

AF:

0.0360

AC:

52591

AN:

1461868

Hom.:

1122

Cov.:

AF XY:

0.0364

AC XY:

26452

AN XY:

727236

show subpopulations

African (AFR)

AF:

0.00585

AC:

196

AN:

33480

American (AMR)

AF:

0.0206

AC:

921

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0255

AC:

667

AN:

26136

East Asian (EAS)

AF:

0.000101

AC:

AN:

39698

South Asian (SAS)

AF:

0.0376

AC:

3242

AN:

86256

European-Finnish (FIN)

AF:

0.0360

AC:

1924

AN:

53414

Middle Eastern (MID)

AF:

0.0345

AC:

199

AN:

5768

European-Non Finnish (NFE)

AF:

0.0391

AC:

43523

AN:

1111998

Other (OTH)

AF:

0.0317

AC:

1915

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

3108

6216

9325

12433

15541

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1640

3280

4920

6560

8200

<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:

0.0267

AC:

4063

AN:

152230

Hom.:

Cov.:

AF XY:

0.0271

AC XY:

2014

AN XY:

74424

show subpopulations

African (AFR)

AF:

0.00703

AC:

292

AN:

41526

American (AMR)

AF:

0.0297

AC:

455

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0280

AC:

AN:

3470

East Asian (EAS)

AF:

0.000387

AC:

AN:

5166

South Asian (SAS)

AF:

0.0313

AC:

151

AN:

4824

European-Finnish (FIN)

AF:

0.0327

AC:

347

AN:

10600

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0377

AC:

2565

AN:

68024

Other (OTH)

AF:

0.0340

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

204

408

611

815

1019

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

138

184

230

<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:

0.0336

Hom.:

362

Bravo

AF:

0.0261

TwinsUK

AF:

0.0345

AC:

128

ALSPAC

AF:

0.0381

AC:

147

ESP6500AA

AF:

0.00817

AC:

ESP6500EA

AF:

0.0385

AC:

331

ExAC

AF:

0.0307

AC:

3733

Asia WGS

AF:

0.0140

AC:

AN:

3478

EpiCase

AF:

0.0376

EpiControl

AF:

0.0388

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.79

CADD

Benign

7.9

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.045

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.60

MetaRNN

Benign

0.0022

MetaSVM

Benign

-0.93

MutationAssessor

Benign

1.1

PhyloP100

-0.33

PrimateAI

Benign

0.30

PROVEAN

Benign

-2.2

REVEL

Benign

0.026

Sift

Benign

0.30

Sift4G

Benign

0.27

Polyphen

0.0090

Vest4

0.033

MPC

0.25

ClinPred

0.0017

GERP RS

-3.1

Varity_R

0.15

gMVP

0.057

Mutation Taster

=98/2

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over