Variant 19-11831690-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_152357.3(ZNF440):c.514A>T(p.Asn172Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,461,570 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

ZNF440
NM_152357.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0880

Variant links:

Genes affected

ZNF440 (HGNC:20874): (zinc finger protein 440) Predicted to enable DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Predicted to be involved in negative regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF440 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.016517818).

BP6

Variant 19-11831690-A-T is Benign according to our data. Variant chr19-11831690-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 2274816.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF440	NM_152357.3 link	c.514A>T	p.Asn172Tyr	missense_variant	4/4	ENST00000304060.10	NP_689570.2	Q8IYI8
ZNF440	XM_005259731.5 link	c.523A>T	p.Asn175Tyr	missense_variant	4/4		XP_005259788.1
ZNF440	XM_047438145.1 link	c.520A>T	p.Asn174Tyr	missense_variant	4/4		XP_047294101.1
ZNF440	XM_017026254.2 link	c.148A>T	p.Asn50Tyr	missense_variant	3/3		XP_016881743.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZNF440	ENST00000304060.10 link	c.514A>T	p.Asn172Tyr	missense_variant	4/4	1	NM_152357.3	ENSP00000305373.5	Q8IYI8
ZNF440	ENST00000427505.5 link	c.523A>T	p.Asn175Tyr	missense_variant	4/4	3		ENSP00000393489.1	C9JV94
ZNF440	ENST00000457526.1 link	c.148A>T	p.Asn50Tyr	missense_variant	3/3	4		ENSP00000404425.1	C9JG89
ZNF440	ENST00000414255.1 link	c.*12A>T		downstream_gene_variant		2		ENSP00000411974.1	C9J3D9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000119

AC:

AN:

251198

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135846

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000616

AC:

AN:

1461570

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727068

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:

0.00

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.00000540

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 31, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.045

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.75

CADD

Benign

0.066

DANN

Benign

0.18

DEOGEN2

Benign

0.0018

T;.;.

Eigen

Benign

-2.1

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.0

LIST_S2

Benign

0.073

T;T;T

M_CAP

Benign

0.00078

MetaRNN

Benign

0.017

T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-3.4

N;.;.

PrimateAI

Benign

0.27

PROVEAN

Benign

7.4

N;N;N

REVEL

Benign

0.044

Sift

Benign

1.0

T;T;T

Sift4G

Benign

1.0

T;T;T

Polyphen

0.0010

B;.;.

Vest4

0.080

MutPred

0.41

Gain of phosphorylation at N172 (P = 0.05);.;.;

MVP

0.17

MPC

0.045

ClinPred

0.042

GERP RS

-1.9

Varity_R

0.026

gMVP

0.026

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