Variant 19-11778365-C-A 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_152355.3(ZNF441):c.166C>A(p.Gln56Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000414 in 1,547,296 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00024 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000020 ( 0 hom. )

Consequence

ZNF441
NM_152355.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.350

Variant links:

Genes affected

ZNF441 (HGNC:20875): (zinc finger protein 441) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II transcription 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]

ZNF441 links:

Genome browser will be placed here

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=0.0432868).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF441	NM_152355.3 linkuse as main transcript	c.166C>A	p.Gln56Lys	missense_variant	3/4	ENST00000357901.5	NP_689568.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF441	ENST00000357901.5 linkuse as main transcript	c.166C>A	p.Gln56Lys	missense_variant	3/4	3	NM_152355.3	ENSP00000350576	P1	Q8N8Z8-1
ZNF441	ENST00000409902.5 linkuse as main transcript	c.*95C>A		3_prime_UTR_variant, NMD_transcript_variant	4/5	2		ENSP00000386658

Frequencies

GnomAD3 genomes

AF:

0.000237

AC:

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000676

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

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:

0.0000441

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000192

AC:

AN:

156082

Hom.:

AF XY:

0.00

AC XY:

AN XY:

82528

show subpopulations

Gnomad AFR exome

AF:

0.000249

Gnomad AMR exome

AF:

0.0000416

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

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:

0.0000201

AC:

AN:

1395106

Hom.:

Cov.:

AF XY:

0.0000189

AC XY:

AN XY:

688046

show subpopulations

Gnomad4 AFR exome

AF:

0.000542

Gnomad4 AMR exome

AF:

0.0000286

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000128

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000557

Gnomad4 OTH exome

AF:

0.0000519

GnomAD4 genome

AF:

0.000237

AC:

AN:

152190

Hom.:

Cov.:

AF XY:

0.000229

AC XY:

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.000676

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000114

Hom.:

Bravo

AF:

0.000200

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

Apr 10, 2023

The c.166C>A (p.Q56K) alteration is located in exon 3 (coding exon 3) of the ZNF441 gene. This alteration results from a C to A substitution at nucleotide position 166, causing the glutamine (Q) at amino acid position 56 to be replaced by a lysine (K). 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

0.11

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.68

CADD

Benign

0.17

DANN

Benign

0.43

DEOGEN2

Benign

0.021

Eigen

Benign

-1.9

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.0056

LIST_S2

Benign

0.14

M_CAP

Benign

0.00066

MetaRNN

Benign

0.043

MetaSVM

Benign

-0.92

MutationAssessor

Benign

2.0

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.34

PROVEAN

Benign

-1.6

REVEL

Benign

0.017

Sift

Benign

0.12

Sift4G

Benign

0.33

Polyphen

0.0

Vest4

0.090

MVP

0.19

MPC

0.40

ClinPred

0.019

GERP RS

-3.1

Varity_R

0.079

gMVP

0.11

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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