dbSNP rs6073972: ZNF335:c.1646+411G>C (chr20-45961659-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_022095.4(ZNF335):c.1646+411G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 163,016 control chromosomes in the GnomAD database, including 1,785 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.13 ( 1638 hom., cov: 31)

Exomes 𝑓: 0.15 ( 147 hom. )

Consequence

ZNF335
NM_022095.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.190

Publications

14 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.192 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022095.4. 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
	ZNF335	NM_022095.4	MANE Select	c.1646+411G>C		intron	N/A	NP_071378.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ZNF335	ENST00000322927.3	TSL:1 MANE Select	c.1646+411G>C	intron	N/A	ENSP00000325326.2
ZNF335	ENST00000944756.1		c.1646+411G>C	intron	N/A	ENSP00000614815.1
ZNF335	ENST00000862676.1		c.1643+411G>C	intron	N/A	ENSP00000532735.1

Frequencies

GnomAD3 genomes

AF:

0.131

AC:

19863

AN:

151992

Hom.:

1638

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0382

Gnomad AMI

AF:

0.187

Gnomad AMR

AF:

0.117

Gnomad ASJ

AF:

0.185

Gnomad EAS

AF:

0.0250

Gnomad SAS

AF:

0.202

Gnomad FIN

AF:

0.150

Gnomad MID

AF:

0.146

Gnomad NFE

AF:

0.186

Gnomad OTH

AF:

0.140

GnomAD4 exome

AF:

0.149

AC:

1621

AN:

10906

Hom.:

147

Cov.:

AF XY:

0.151

AC XY:

871

AN XY:

5766

show subpopulations

African (AFR)

AF:

0.0326

AC:

AN:

552

American (AMR)

AF:

0.131

AC:

154

AN:

1172

Ashkenazi Jewish (ASJ)

AF:

0.185

AC:

AN:

308

East Asian (EAS)

AF:

0.0191

AC:

AN:

682

South Asian (SAS)

AF:

0.159

AC:

AN:

590

European-Finnish (FIN)

AF:

0.179

AC:

AN:

302

Middle Eastern (MID)

AF:

0.133

AC:

AN:

European-Non Finnish (NFE)

AF:

0.171

AC:

1145

AN:

6710

Other (OTH)

AF:

0.146

AC:

AN:

560

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.518

Heterozygous variant carriers

153

230

306

383

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.131

AC:

19862

AN:

152110

Hom.:

1638

Cov.:

AF XY:

0.131

AC XY:

9707

AN XY:

74364

show subpopulations

African (AFR)

AF:

0.0383

AC:

1588

AN:

41498

American (AMR)

AF:

0.117

AC:

1782

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.185

AC:

641

AN:

3466

East Asian (EAS)

AF:

0.0247

AC:

128

AN:

5184

South Asian (SAS)

AF:

0.202

AC:

975

AN:

4818

European-Finnish (FIN)

AF:

0.150

AC:

1584

AN:

10576

Middle Eastern (MID)

AF:

0.133

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.186

AC:

12658

AN:

67972

Other (OTH)

AF:

0.141

AC:

297

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

850

1700

2550

3400

4250

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

222

444

666

888

1110

<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:

0.0867

Hom.:

121

Bravo

AF:

0.123

Asia WGS

AF:

0.118

AC:

410

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

3.1

(source)

DANN

Benign

0.69

PhyloP100

0.19

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over