Variant 6-57147646-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001031623.3(ZNF451):c.1561C>A(p.His521Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,122 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

ZNF451
NM_001031623.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.22

Variant links:

Genes affected

ZNF451 (HGNC:21091): (zinc finger protein 451) Enables SUMO ligase activity and transcription corepressor activity. Involved in negative regulation of nitrogen compound metabolic process; negative regulation of transforming growth factor beta receptor signaling pathway; and protein sumoylation. Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF451 links:

ZNF451-AS1 (HGNC:53824): (ZNF451 regulatory antisense RNA 1)

ZNF451-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.767

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF451	NM_001031623.3 linkuse as main transcript	c.1561C>A	p.His521Asn	missense_variant	10/15	ENST00000370706.9
ZNF451-AS1	NR_110742.1 linkuse as main transcript	n.234+23359G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF451	ENST00000370706.9 linkuse as main transcript	c.1561C>A	p.His521Asn	missense_variant	10/15	1	NM_001031623.3	P2	Q9Y4E5-1
ZNF451-AS1	ENST00000416069.6 linkuse as main transcript	n.443+23359G>T		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152122

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152122

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74296

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

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

Dec 14, 2022

The c.1561C>A (p.H521N) alteration is located in exon 10 (coding exon 10) of the ZNF451 gene. This alteration results from a C to A substitution at nucleotide position 1561, causing the histidine (H) at amino acid position 521 to be replaced by an asparagine (N). 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

Pathogenic

0.99

BayesDel_addAF

Benign

-0.021

BayesDel_noAF

Benign

-0.27

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.46

T;.;T

Eigen

Pathogenic

1.0

Eigen_PC

Pathogenic

0.93

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.87

D;D;D

M_CAP

Uncertain

0.094

MetaRNN

Pathogenic

0.77

D;D;D

MetaSVM

Benign

-0.62

MutationAssessor

Pathogenic

3.8

H;H;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Pathogenic

0.84

PROVEAN

Uncertain

-3.7

D;D;D

REVEL

Uncertain

0.43

Sift

Uncertain

0.0020

D;D;D

Sift4G

Uncertain

0.0090

D;D;D

Polyphen

1.0

D;D;D

Vest4

0.81

MutPred

0.49

Gain of MoRF binding (P = 0.1498);Gain of MoRF binding (P = 0.1498);Gain of MoRF binding (P = 0.1498);

MVP

0.65

MPC

0.77

ClinPred

0.99

GERP RS

5.4

Varity_R

0.71

gMVP

0.70

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