rs4465830

Variant names:

• chr20-45956781-A-G
• rs4465830
• NM_022095.4:c.2442+805T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022095.4(ZNF335):​c.2442+805T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.131 in 152,192 control chromosomes in the GnomAD database, including 1,650 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 (1650 hom., cov: 31)
• Consequence: ZNF335 NM_022095.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0920
• Publications: 15 publications found

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)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.192 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF335	NM_022095.4	c.2442+805T>C		intron_variant	Intron 17 of 27	ENST00000322927.3	NP_071378.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF335	ENST00000322927.3	c.2442+805T>C		intron_variant	Intron 17 of 27	1	NM_022095.4	ENSP00000325326.2

Frequencies

GnomAD3 genomes AF: 0.131 AC: 19923 AN: 152074 Hom.: 1650 Cov.: 31

Gnomad AFR AF: 0.0388

Gnomad AMI AF: 0.189

Gnomad AMR AF: 0.117

Gnomad ASJ AF: 0.185

Gnomad EAS AF: 0.0248

Gnomad SAS AF: 0.202

Gnomad FIN AF: 0.150

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.186

Gnomad OTH AF: 0.140

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.131 AC: 19922 AN: 152192 Hom.: 1650 Cov.: 31 AF XY: 0.131 AC XY: 9745 AN XY: 74408

African (AFR) AF: 0.0388 AC: 1613 AN: 41542

American (AMR) AF: 0.117 AC: 1792 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.185 AC: 643 AN: 3468

East Asian (EAS) AF: 0.0245 AC: 127 AN: 5188

South Asian (SAS) AF: 0.203 AC: 978 AN: 4826

European-Finnish (FIN) AF: 0.150 AC: 1585 AN: 10582

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.186 AC: 12674 AN: 67974

Other (OTH) AF: 0.141 AC: 298 AN: 2116

Alfa AF: 0.154 Hom.: 256

Bravo AF: 0.123

Asia WGS AF: 0.119 AC: 411 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	8.2
DANN	Benign	0.39
PhyloP100		0.092
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4465830; hg19: chr20-44585420;