Variant 19-11830406-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000304060.10(ZNF440):c.127T>A(p.Leu43Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.364 in 1,612,846 control chromosomes in the GnomAD database, including 109,270 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.38 ( 11325 hom., cov: 32)

Exomes 𝑓: 0.36 ( 97945 hom. )

Consequence

ZNF440
ENST00000304060.10 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.06

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 Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=7.017553E-4).

BP6

Variant 19-11830406-T-A is Benign according to our data. Variant chr19-11830406-T-A is described in ClinVar as [Benign]. Clinvar id is 769959.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.457 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF440	NM_152357.3 linkuse as main transcript	c.127T>A	p.Leu43Ile	missense_variant	2/4	ENST00000304060.10	NP_689570.2	Q8IYI8
ZNF440	XM_005259731.5 linkuse as main transcript	c.136T>A	p.Leu46Ile	missense_variant	2/4		XP_005259788.1
ZNF440	XM_047438145.1 linkuse as main transcript	c.133T>A	p.Leu45Ile	missense_variant	2/4		XP_047294101.1
ZNF440	XM_017026254.2 linkuse as main transcript	c.-236-211T>A		intron_variant			XP_016881743.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF440	ENST00000304060.10 linkuse as main transcript	c.127T>A	p.Leu43Ile	missense_variant	2/4	1	NM_152357.3	ENSP00000305373.5		Q8IYI8

Frequencies

GnomAD3 genomes

AF:

0.379

AC:

57578

AN:

151960

Hom.:

11307

Cov.:

show subpopulations

Gnomad AFR

AF:

0.462

Gnomad AMI

AF:

0.332

Gnomad AMR

AF:

0.327

Gnomad ASJ

AF:

0.362

Gnomad EAS

AF:

0.152

Gnomad SAS

AF:

0.246

Gnomad FIN

AF:

0.324

Gnomad MID

AF:

0.449

Gnomad NFE

AF:

0.377

Gnomad OTH

AF:

0.369

GnomAD3 exomes

AF:

0.337

AC:

84161

AN:

250036

Hom.:

15019

AF XY:

0.334

AC XY:

45230

AN XY:

135370

show subpopulations

Gnomad AFR exome

AF:

0.465

Gnomad AMR exome

AF:

0.313

Gnomad ASJ exome

AF:

0.354

Gnomad EAS exome

AF:

0.159

Gnomad SAS exome

AF:

0.250

Gnomad FIN exome

AF:

0.325

Gnomad NFE exome

AF:

0.378

Gnomad OTH exome

AF:

0.349

GnomAD4 exome

AF:

0.362

AC:

528936

AN:

1460768

Hom.:

97945

Cov.:

AF XY:

0.359

AC XY:

261145

AN XY:

726728

show subpopulations

Gnomad4 AFR exome

AF:

0.469

Gnomad4 AMR exome

AF:

0.314

Gnomad4 ASJ exome

AF:

0.355

Gnomad4 EAS exome

AF:

0.130

Gnomad4 SAS exome

AF:

0.255

Gnomad4 FIN exome

AF:

0.329

Gnomad4 NFE exome

AF:

0.380

Gnomad4 OTH exome

AF:

0.353

GnomAD4 genome

AF:

0.379

AC:

57634

AN:

152078

Hom.:

11325

Cov.:

AF XY:

0.372

AC XY:

27680

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.462

Gnomad4 AMR

AF:

0.327

Gnomad4 ASJ

AF:

0.362

Gnomad4 EAS

AF:

0.152

Gnomad4 SAS

AF:

0.246

Gnomad4 FIN

AF:

0.324

Gnomad4 NFE

AF:

0.377

Gnomad4 OTH

AF:

0.368

Alfa

AF:

0.331

Hom.:

2614

Bravo

AF:

0.385

ExAC

AF:

0.346

AC:

42009

EpiCase

AF:

0.373

EpiControl

AF:

0.371

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.70

CADD

Benign

0.028

DANN

Benign

0.051

DEOGEN2

Benign

0.0054

T;.;.;.

Eigen

Benign

-2.9

Eigen_PC

Benign

-3.0

FATHMM_MKL

Benign

0.0015

LIST_S2

Benign

0.54

T;T;T;T

MetaRNN

Benign

0.00070

T;T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.5

L;.;.;.

MutationTaster

Benign

1.0

PrimateAI

Benign

0.31

PROVEAN

Benign

1.4

N;N;.;N

REVEL

Benign

0.014

Sift

Benign

1.0

T;T;.;T

Sift4G

Benign

1.0

T;T;T;T

Polyphen

0.0

B;.;.;.

Vest4

0.043

MPC

0.041

ClinPred

0.00095

GERP RS

-3.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.067

gMVP

0.011

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