Variant 5-178712378-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_005649.3(ZNF354A):c.1500G>C(p.Gly500Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00419 in 1,601,774 control chromosomes in the GnomAD database, including 86 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0088 ( 15 hom., cov: 33)

Exomes 𝑓: 0.0037 ( 71 hom. )

Consequence

ZNF354A
NM_005649.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.08

Variant links:

Genes affected

ZNF354A (HGNC:11628): (zinc finger protein 354A) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Located in cytosol; nucleolus; and nucleoplasm. Biomarker of in situ carcinoma and seminoma. [provided by Alliance of Genome Resources, Apr 2022]

ZNF354A links:

ENSG00000285978 (HGNC:):

ENSG00000285978 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.61).

BP6

Variant 5-178712378-C-G is Benign according to our data. Variant chr5-178712378-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 2656128.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-1.08 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 15 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF354A	NM_005649.3 linkuse as main transcript	c.1500G>C	p.Gly500Gly	synonymous_variant	5/5	ENST00000335815.7	NP_005640.2	O60765V9HWI2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF354A	ENST00000335815.7 linkuse as main transcript	c.1500G>C	p.Gly500Gly	synonymous_variant	5/5	1	NM_005649.3	ENSP00000337122.2		O60765
ENSG00000285978	ENST00000638723.1 linkuse as main transcript	n.257-5206G>C		intron_variant		5		ENSP00000492050.1		A0A1W2PQE6

Frequencies

GnomAD3 genomes

AF:

0.00885

AC:

1339

AN:

151350

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00237

Gnomad AMI

AF:

0.0143

Gnomad AMR

AF:

0.0107

Gnomad ASJ

AF:

0.0104

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00187

Gnomad FIN

AF:

0.00293

Gnomad MID

AF:

0.0191

Gnomad NFE

AF:

0.0143

Gnomad OTH

AF:

0.00767

GnomAD3 exomes

AF:

0.00216

AC:

541

AN:

250714

Hom.:

AF XY:

0.00200

AC XY:

271

AN XY:

135534

show subpopulations

Gnomad AFR exome

AF:

0.000677

Gnomad AMR exome

AF:

0.00316

Gnomad ASJ exome

AF:

0.00179

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.000751

Gnomad FIN exome

AF:

0.000185

Gnomad NFE exome

AF:

0.00307

Gnomad OTH exome

AF:

0.00458

GnomAD4 exome

AF:

0.00371

AC:

5376

AN:

1450306

Hom.:

Cov.:

AF XY:

0.00374

AC XY:

2701

AN XY:

721696

show subpopulations

Gnomad4 AFR exome

AF:

0.000747

Gnomad4 AMR exome

AF:

0.00455

Gnomad4 ASJ exome

AF:

0.00622

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00164

Gnomad4 FIN exome

AF:

0.00285

Gnomad4 NFE exome

AF:

0.00395

Gnomad4 OTH exome

AF:

0.00477

GnomAD4 genome

AF:

0.00883

AC:

1338

AN:

151468

Hom.:

Cov.:

AF XY:

0.00862

AC XY:

639

AN XY:

74092

show subpopulations

Gnomad4 AFR

AF:

0.00236

Gnomad4 AMR

AF:

0.0107

Gnomad4 ASJ

AF:

0.0104

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00187

Gnomad4 FIN

AF:

0.00293

Gnomad4 NFE

AF:

0.0143

Gnomad4 OTH

AF:

0.00759

Alfa

AF:

0.00586

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2022

ZNF354A: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.61

CADD

Benign

6.2

DANN

Benign

0.71

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over