20-45948675-C-T

Position:

• chr20-45948675-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_022095.4(ZNF335):​c.*278G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 448,752 control chromosomes in the GnomAD database, including 5,988 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.17 (2514 hom., cov: 33)
  • Exomes 𝑓: 0.14 (3474 hom.)
• Consequence: ZNF335 NM_022095.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.441

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 20-45948675-C-T is Benign according to our data. Variant chr20-45948675-C-T is described in ClinVar as [Benign]. Clinvar id is 1231704.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.312 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF335	NM_022095.4	c.*278G>A		3_prime_UTR_variant	28/28	ENST00000322927.3
ZNF335	XM_005260504.5	c.*278G>A		3_prime_UTR_variant	27/27
ZNF335	XM_047440363.1	c.*278G>A		3_prime_UTR_variant	27/27

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF335	ENST00000322927.3	c.*278G>A		3_prime_UTR_variant	28/28	1	NM_022095.4	P1

Frequencies

GnomAD3 genomes AF: 0.166 AC: 25179 AN: 152042 Hom.: 2511 Cov.: 33

Gnomad AFR AF: 0.273

Gnomad AMI AF: 0.0877

Gnomad AMR AF: 0.0961

Gnomad ASJ AF: 0.109

Gnomad EAS AF: 0.324

Gnomad SAS AF: 0.188

Gnomad FIN AF: 0.125

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.114

Gnomad OTH AF: 0.142

GnomAD4 exome AF: 0.137 AC: 40618 AN: 296590 Hom.: 3474 Cov.: 3 AF XY: 0.140 AC XY: 22109 AN XY: 157834

Gnomad4 AFR exome AF: 0.265

Gnomad4 AMR exome AF: 0.0944

Gnomad4 ASJ exome AF: 0.106

Gnomad4 EAS exome AF: 0.315

Gnomad4 SAS exome AF: 0.176

Gnomad4 FIN exome AF: 0.111

Gnomad4 NFE exome AF: 0.112

Gnomad4 OTH exome AF: 0.129

GnomAD4 genome AF: 0.166 AC: 25202 AN: 152162 Hom.: 2514 Cov.: 33 AF XY: 0.167 AC XY: 12409 AN XY: 74366

Gnomad4 AFR AF: 0.273

Gnomad4 AMR AF: 0.0962

Gnomad4 ASJ AF: 0.109

Gnomad4 EAS AF: 0.325

Gnomad4 SAS AF: 0.187

Gnomad4 FIN AF: 0.125

Gnomad4 NFE AF: 0.114

Gnomad4 OTH AF: 0.139

Alfa AF: 0.115 Hom.: 1845

Bravo AF: 0.169

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 27, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	6.4
DANN	Benign	0.62
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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

Other links and lift over

dbSNP: rs3363; hg19: chr20-44577314;