rs3848719

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_022095.4(ZNF335):c.642C>T(p.Ser214Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.392 in 1,612,760 control chromosomes in the GnomAD database, including 134,038 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.32 ( 9230 hom., cov: 32)

Exomes 𝑓: 0.40 ( 124808 hom. )

Consequence

ZNF335
NM_022095.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 1.19

Publications

28 publications found

Variant links:

Genes affected

ZNF335 (HGNC:15807): (zinc finger protein 335) The protein encoded by this gene enhances transcriptional activation by ligand-bound nuclear hormone receptors. However, it does this not by direct interaction with the receptor, but by direct interaction with the nuclear hormone receptor transcriptional coactivator NRC. The encoded protein may function by altering local chromatin structure. [provided by RefSeq, Jul 2008]

ZNF335 Gene-Disease associations (from GenCC):

microcephalic primordial dwarfism due to ZNF335 deficiency
Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)

ZNF335 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BP6

Variant 20-45967906-G-A is Benign according to our data. Variant chr20-45967906-G-A is described in ClinVar as Benign. ClinVar VariationId is 130807.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.19 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.428 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF335	NM_022095.4 link	c.642C>T	p.Ser214Ser	synonymous_variant	Exon 5 of 28	ENST00000322927.3	NP_071378.1	Q9H4Z2-1Q8IW09

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ZNF335	ENST00000322927.3 link	c.642C>T	p.Ser214Ser	synonymous_variant	Exon 5 of 28	1	NM_022095.4	ENSP00000325326.2	Q9H4Z2-1
ZNF335	ENST00000476822.1 link	n.975C>T		non_coding_transcript_exon_variant	Exon 3 of 5	2
ZNF335	ENST00000494955.1 link	n.953C>T		non_coding_transcript_exon_variant	Exon 1 of 2	2

Frequencies

GnomAD3 genomes

AF:

0.317

AC:

48134

AN:

152024

Hom.:

9232

Cov.:

show subpopulations

Gnomad AFR

AF:

0.133

Gnomad AMI

AF:

0.519

Gnomad AMR

AF:

0.372

Gnomad ASJ

AF:

0.323

Gnomad EAS

AF:

0.00270

Gnomad SAS

AF:

0.217

Gnomad FIN

AF:

0.384

Gnomad MID

AF:

0.462

Gnomad NFE

AF:

0.432

Gnomad OTH

AF:

0.348

GnomAD2 exomes

AF:

0.328

AC:

81521

AN:

248286

AF XY:

0.333

show subpopulations

Gnomad AFR exome

AF:

0.127

Gnomad AMR exome

AF:

0.289

Gnomad ASJ exome

AF:

0.328

Gnomad EAS exome

AF:

0.00115

Gnomad FIN exome

AF:

0.383

Gnomad NFE exome

AF:

0.437

Gnomad OTH exome

AF:

0.377

GnomAD4 exome

AF:

0.400

AC:

584389

AN:

1460618

Hom.:

124808

Cov.:

AF XY:

0.396

AC XY:

287838

AN XY:

726596

show subpopulations

African (AFR)

AF:

0.121

AC:

4051

AN:

33480

American (AMR)

AF:

0.299

AC:

13354

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.323

AC:

8430

AN:

26130

East Asian (EAS)

AF:

0.000730

AC:

AN:

39700

South Asian (SAS)

AF:

0.233

AC:

20137

AN:

86256

European-Finnish (FIN)

AF:

0.397

AC:

20740

AN:

52216

Middle Eastern (MID)

AF:

0.416

AC:

2400

AN:

5768

European-Non Finnish (NFE)

AF:

0.443

AC:

492731

AN:

1111972

Other (OTH)

AF:

0.373

AC:

22517

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

22873

45745

68618

91490

114363

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14486

28972

43458

57944

72430

<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:

0.316

AC:

48132

AN:

152142

Hom.:

9230

Cov.:

AF XY:

0.311

AC XY:

23166

AN XY:

74370

show subpopulations

African (AFR)

AF:

0.133

AC:

5515

AN:

41530

American (AMR)

AF:

0.371

AC:

5669

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.323

AC:

1121

AN:

3468

East Asian (EAS)

AF:

0.00270

AC:

AN:

5178

South Asian (SAS)

AF:

0.218

AC:

1052

AN:

4822

European-Finnish (FIN)

AF:

0.384

AC:

4065

AN:

10584

Middle Eastern (MID)

AF:

0.463

AC:

136

AN:

294

European-Non Finnish (NFE)

AF:

0.432

AC:

29365

AN:

67974

Other (OTH)

AF:

0.343

AC:

723

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1567

3134

4700

6267

7834

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

460

920

1380

1840

2300

<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:

0.375

Hom.:

5148

Bravo

AF:

0.305

Asia WGS

AF:

0.104

AC:

367

AN:

3478

EpiCase

AF:

0.432

EpiControl

AF:

0.438

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 17, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:2

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

May 17, 2016

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Microcephalic primordial dwarfism due to ZNF335 deficiency

Benign:1

Dec 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

9.5

(source)

DANN

Benign

0.67

PhyloP100

1.2

Mutation Taster

=100/0

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over