Variant chr20-45948675-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_022095.4(ZNF335):c.*278G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00133 in 449,044 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0031 ( 2 hom., cov: 33)

Exomes 𝑓: 0.00043 ( 0 hom. )

Consequence

ZNF335
NM_022095.4 3_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.441

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP6

Variant 20-45948675-C-G is Benign according to our data. Variant chr20-45948675-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 1197755.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00308 (469/152198) while in subpopulation AFR AF= 0.0107 (445/41528). AF 95% confidence interval is 0.00989. There are 2 homozygotes in gnomad4. There are 226 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
ZNF335	NM_022095.4 linkuse as main transcript	c.*278G>C	3_prime_UTR_variant	28/28	ENST00000322927.3
ZNF335	XM_005260504.5 linkuse as main transcript	c.*278G>C	3_prime_UTR_variant	27/27
ZNF335	XM_047440363.1 linkuse as main transcript	c.*278G>C	3_prime_UTR_variant	27/27

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF335	ENST00000322927.3 linkuse as main transcript	c.*278G>C		3_prime_UTR_variant	28/28	1	NM_022095.4	P1	Q9H4Z2-1

Frequencies

GnomAD3 genomes

AF:

0.00308

AC:

469

AN:

152078

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0107

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000916

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00144

GnomAD4 exome

AF:

0.000431

AC:

128

AN:

296846

Hom.:

Cov.:

AF XY:

0.000373

AC XY:

AN XY:

157972

show subpopulations

Gnomad4 AFR exome

AF:

0.0101

Gnomad4 AMR exome

AF:

0.000789

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000693

Gnomad4 OTH exome

AF:

0.00104

GnomAD4 genome

AF:

0.00308

AC:

469

AN:

152198

Hom.:

Cov.:

AF XY:

0.00304

AC XY:

226

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.0107

Gnomad4 AMR

AF:

0.000915

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00142

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

GeneDx

Dec 05, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

3.2

DANN

Benign

0.65

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