rs6073972

Positions:

• chr20-45961659-C-G
• chr20-45961659-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.190

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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF335	NM_022095.4	c.1646+411G>C		intron_variant		ENST00000322927.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF335	ENST00000322927.3	c.1646+411G>C		intron_variant		1	NM_022095.4	P1
ZNF335	ENST00000475002.1	n.1568G>C		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes AF: 0.131 AC: 19863 AN: 151992 Hom.: 1638 Cov.: 31

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.: 0 AF XY: 0.151 AC XY: 871 AN XY: 5766

Gnomad4 AFR exome AF: 0.0326

Gnomad4 AMR exome AF: 0.131

Gnomad4 ASJ exome AF: 0.185

Gnomad4 EAS exome AF: 0.0191

Gnomad4 SAS exome AF: 0.159

Gnomad4 FIN exome AF: 0.179

Gnomad4 NFE exome AF: 0.171

Gnomad4 OTH exome AF: 0.146

GnomAD4 genome AF: 0.131 AC: 19862 AN: 152110 Hom.: 1638 Cov.: 31 AF XY: 0.131 AC XY: 9707 AN XY: 74364

Gnomad4 AFR AF: 0.0383

Gnomad4 AMR AF: 0.117

Gnomad4 ASJ AF: 0.185

Gnomad4 EAS AF: 0.0247

Gnomad4 SAS AF: 0.202

Gnomad4 FIN AF: 0.150

Gnomad4 NFE AF: 0.186

Gnomad4 OTH AF: 0.141

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.1
DANN	Benign	0.69

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: rs6073972; hg19: chr20-44590298;