Variant 4-442035-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_133474.4(ZNF721):c.2432G>A(p.Cys811Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,682 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: 0.0000055 ( 0 hom. )

Consequence

ZNF721
NM_133474.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.91

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:31): (ATP binding cassette subfamily A member 11, pseudogene)

ABCA11P links:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF721	NM_133474.4 linkuse as main transcript	c.2432G>A	p.Cys811Tyr	missense_variant	3/3	ENST00000511833.3	NP_597731.2
ABCA11P	NR_002451.2 linkuse as main transcript	n.357-15062G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF721	ENST00000511833.3 linkuse as main transcript	c.2432G>A	p.Cys811Tyr	missense_variant	3/3	4	NM_133474.4	ENSP00000428878	P1	Q8TF20-2
ABCA11P	ENST00000451020.6 linkuse as main transcript	n.277-15062G>A		intron_variant, non_coding_transcript_variant		2
	ENST00000631198.1 linkuse as main transcript	n.139-11421C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000120

AC:

AN:

249316

Hom.:

AF XY:

0.00000739

AC XY:

AN XY:

135282

show subpopulations

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:

0.0000981

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000547

AC:

AN:

1461682

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

727138

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000812

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 20, 2024

The c.2432G>A (p.C811Y) alteration is located in exon 3 (coding exon 2) of the ZNF721 gene. This alteration results from a G to A substitution at nucleotide position 2432, causing the cysteine (C) at amino acid position 811 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.50

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.19

CADD

Benign

DANN

Benign

0.89

DEOGEN2

Benign

0.15

T;.

Eigen

Benign

0.10

Eigen_PC

Benign

-0.24

FATHMM_MKL

Benign

0.000060

LIST_S2

Benign

0.61

T;T

M_CAP

Benign

0.0033

MetaRNN

Uncertain

0.64

D;D

MetaSVM

Uncertain

-0.012

MutationAssessor

Pathogenic

3.8

H;.

MutationTaster

Benign

1.0

D;N;N

PrimateAI

Uncertain

0.51

PROVEAN

Pathogenic

-7.3

D;D

REVEL

Benign

0.28

Sift

Uncertain

0.0050

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;D

Vest4

0.31

MutPred

0.71

Loss of glycosylation at K795 (P = 0.0273);.;

MVP

0.47

MPC

0.12

ClinPred

0.73

GERP RS

0.50

Varity_R

0.35

gMVP

0.17

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