Variant 4-442244-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_133474.4(ZNF721):c.2223C>T(p.Asn741Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000262 in 1,612,614 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0011 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00018 ( 0 hom. )

Consequence

ZNF721
NM_133474.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.71

Variant links:

Genes affected

ZNF721 (HGNC:29425): (zinc finger protein 721) Predicted to enable DNA-binding transcription activator 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. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF721 links:

ABCA11P (HGNC:):

ABCA11P links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.98).

BP6

Variant 4-442244-G-A is Benign according to our data. Variant chr4-442244-G-A is described in ClinVar as [Benign]. Clinvar id is 737100.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-3.71 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF721	NM_133474.4 linkuse as main transcript	c.2223C>T	p.Asn741Asn	synonymous_variant	3/3	ENST00000511833.3	NP_597731.2	Q8TF20-2
ABCA11P	NR_002451.2 linkuse as main transcript	n.357-15271C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF721	ENST00000511833.3 linkuse as main transcript	c.2223C>T	p.Asn741Asn	synonymous_variant	3/3	4	NM_133474.4	ENSP00000428878.1		Q8TF20-2

Frequencies

GnomAD3 genomes

AF:

0.00108

AC:

164

AN:

151798

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00341

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000591

Gnomad ASJ

AF:

0.000289

Gnomad EAS

AF:

0.000581

Gnomad SAS

AF:

0.000836

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.000506

AC:

125

AN:

247032

Hom.:

AF XY:

0.000410

AC XY:

AN XY:

134002

show subpopulations

Gnomad AFR exome

AF:

0.00441

Gnomad AMR exome

AF:

0.000527

Gnomad ASJ exome

AF:

0.000100

Gnomad EAS exome

AF:

0.00129

Gnomad SAS exome

AF:

0.000262

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000537

Gnomad OTH exome

AF:

0.000167

GnomAD4 exome

AF:

0.000176

AC:

257

AN:

1460696

Hom.:

Cov.:

AF XY:

0.000176

AC XY:

128

AN XY:

726578

show subpopulations

Gnomad4 AFR exome

AF:

0.00332

Gnomad4 AMR exome

AF:

0.000538

Gnomad4 ASJ exome

AF:

0.000153

Gnomad4 EAS exome

AF:

0.000579

Gnomad4 SAS exome

AF:

0.000383

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000423

Gnomad4 OTH exome

AF:

0.000232

GnomAD4 genome

AF:

0.00109

AC:

165

AN:

151918

Hom.:

Cov.:

AF XY:

0.00105

AC XY:

AN XY:

74252

show subpopulations

Gnomad4 AFR

AF:

0.00343

Gnomad4 AMR

AF:

0.000590

Gnomad4 ASJ

AF:

0.000289

Gnomad4 EAS

AF:

0.000583

Gnomad4 SAS

AF:

0.000836

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000748

Hom.:

Bravo

AF:

0.00136

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 13, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.98

CADD

Benign

5.2

DANN

Benign

0.48

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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