rs772015167

chr20-45949576-T-G

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_Strong BP6

The NM_022095.4(ZNF335):c.3670-8A>C variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000434 in 1,406,332 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.000080 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000043 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ZNF335 NM_022095.4 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00003835
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:1
• Conservation: PhyloP100: -0.330

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 Likely_benign. Variant got -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant 20-45949576-T-G is Benign according to our data. Variant chr20-45949576-T-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 437343.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF335	NM_022095.4	c.3670-8A>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000322927.3
ZNF335	XM_005260504.5	c.3667-8A>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant
ZNF335	XM_047440363.1	c.3670-8A>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF335	ENST00000322927.3	c.3670-8A>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_022095.4	P1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 12 AN: 150034 Hom.: 0 Cov.: 32 FAILED QC

Gnomad AFR AF: 0.000246

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000664

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000214

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000700 AC: 15 AN: 214316 Hom.: 0 AF XY: 0.0000343 AC XY: 4 AN XY: 116506

Gnomad AFR exome AF: 0.000285

Gnomad AMR exome AF: 0.0000679

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000592

Gnomad SAS exome AF: 0.0000375

Gnomad FIN exome AF: 0.0000599

Gnomad NFE exome AF: 0.0000616

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000434 AC: 61 AN: 1406332 Hom.: 0 Cov.: 31 AF XY: 0.0000429 AC XY: 30 AN XY: 699372

Gnomad4 AFR exome AF: 0.000187

Gnomad4 AMR exome AF: 0.000143

Gnomad4 ASJ exome AF: 0.0000802

Gnomad4 EAS exome AF: 0.0000511

Gnomad4 SAS exome AF: 0.0000477

Gnomad4 FIN exome AF: 0.000100

Gnomad4 NFE exome AF: 0.0000290

Gnomad4 OTH exome AF: 0.0000859

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000800 AC: 12 AN: 150034 Hom.: 0 Cov.: 32 AF XY: 0.0000820 AC XY: 6 AN XY: 73132

Gnomad4 AFR AF: 0.000246

Gnomad4 AMR AF: 0.0000664

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000214

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1 Benign:1

Revision: criteria provided, conflicting classifications

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Oct 03, 2016

- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jun 05, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	0.25
Dann	Benign	0.19

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000038
dbscSNV1_RF	Benign	0.060
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: rs772015167; hg19: chr20-44578215; COSMIC: COSV59817784; COSMIC: COSV59817784;