Variant 6-57090269-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001031623.3(ZNF451):c.16T>C(p.Ser6Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,458,914 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 29)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

ZNF451
NM_001031623.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.410

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.037341923).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF451	NM_001031623.3 linkuse as main transcript	c.16T>C	p.Ser6Pro	missense_variant	1/15	ENST00000370706.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF451	ENST00000370706.9 linkuse as main transcript	c.16T>C	p.Ser6Pro	missense_variant	1/15	1	NM_001031623.3	P2	Q9Y4E5-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000409

AC:

AN:

244624

Hom.:

AF XY:

0.00000753

AC XY:

AN XY:

132734

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000549

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000411

AC:

AN:

1458914

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

725644

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000665

GnomAD4 genome

Cov.:

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

Aug 28, 2023

The c.16T>C (p.S6P) alteration is located in exon 1 (coding exon 1) of the ZNF451 gene. This alteration results from a T to C substitution at nucleotide position 16, causing the serine (S) at amino acid position 6 to be replaced by a proline (P). 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

Benign

0.062

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.022

T;T;.;.;.;.;T;.

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.98

FATHMM_MKL

Benign

0.22

LIST_S2

Benign

0.22

T;T;T;T;T;T;T;T

M_CAP

Benign

0.029

MetaRNN

Benign

0.037

T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.41

.;N;N;N;.;.;.;.

MutationTaster

Benign

1.0

N;N;N;N;N;N

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-0.64

N;N;N;N;N;N;N;N

REVEL

Benign

0.044

Sift

Benign

0.043

D;T;T;T;T;D;T;T

Sift4G

Pathogenic

0.0

D;T;T;T;T;D;T;T

Polyphen

0.0

.;B;B;B;.;.;B;.

Vest4

0.098, 0.085, 0.10, 0.10, 0.19

MutPred

0.18

Loss of phosphorylation at S6 (P = 0.0119);Loss of phosphorylation at S6 (P = 0.0119);Loss of phosphorylation at S6 (P = 0.0119);Loss of phosphorylation at S6 (P = 0.0119);Loss of phosphorylation at S6 (P = 0.0119);Loss of phosphorylation at S6 (P = 0.0119);Loss of phosphorylation at S6 (P = 0.0119);Loss of phosphorylation at S6 (P = 0.0119);

MVP

0.42

MPC

0.23

ClinPred

0.047

GERP RS

-4.5

Varity_R

0.098

gMVP

0.091

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