rs1555852178

Positions:

• chr20-45971258-G-GGCCTCT

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PM4

The NM_022095.4(ZNF335):​c.152_153insAGAGGC​(p.Glu50_Ala51dup) variant causes a inframe insertion change. The variant allele was found at a frequency of 0.00000922 in 1,409,766 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000092 (0 hom.)
• Consequence: ZNF335 NM_022095.4 inframe_insertion
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 6.49

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 Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_022095.4.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF335	NM_022095.4	c.152_153insAGAGGC	p.Glu50_Ala51dup	inframe_insertion	2/28	ENST00000322927.3	NP_071378.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF335	ENST00000322927.3	c.152_153insAGAGGC	p.Glu50_Ala51dup	inframe_insertion	2/28	1	NM_022095.4	ENSP00000325326	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.0000244 AC: 4 AN: 164078 Hom.: 0 AF XY: 0.0000443 AC XY: 4 AN XY: 90386

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000395

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000299

Gnomad OTH exome AF: 0.000220

GnomAD4 exome AF: 0.00000922 AC: 13 AN: 1409766 Hom.: 0 Cov.: 35 AF XY: 0.00000860 AC XY: 6 AN XY: 698004

Gnomad4 AFR exome AF: 0.0000925

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000122

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000458

Gnomad4 OTH exome AF: 0.0000341

GnomAD4 genome Cov.: 33

Alfa AF: 0.000102 Hom.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Jul 01, 2016

- -

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

GeneDx

Feb 01, 2022

Not observed at significant frequency in large population cohorts (gnomAD); In-frame insertion of 2 amino acids in a non-repeat region; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1555852178; hg19: chr20-44599897;