Variant 19-56160128-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000337080.8(ZNF444):c.911C>T(p.Ala304Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000654 in 1,482,556 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00044 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00068 ( 1 hom. )

Consequence

ZNF444
ENST00000337080.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.00300

Variant links:

Genes affected

ZNF444 (HGNC:16052): (zinc finger protein 444) This gene encodes a zinc finger protein which activates transcription of a scavenger receptor gene involved in the degradation of acetylated low density lipoprotein (Ac-LDL) (PMID: 11978792). This gene is located in a cluster of zinc finger genes on chromosome 19 at q13.4. A pseudogene of this gene is located on chromosome 15. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]

ZNF444 links:

ZNF444 (HGNC:):

ZNF444 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=0.03530851).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF444	NM_018337.4 linkuse as main transcript	c.911C>T	p.Ala304Val	missense_variant	5/5	ENST00000337080.8	NP_060807.2	Q8N0Y2-1A0A024R4S5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZNF444	ENST00000337080.8 linkuse as main transcript	c.911C>T	p.Ala304Val	missense_variant	5/5	1	NM_018337.4	ENSP00000338860.3	Q8N0Y2-1
ZNF444	ENST00000592949.5 linkuse as main transcript	c.908C>T	p.Ala303Val	missense_variant	5/5	1		ENSP00000468069.1	Q8N0Y2-2
ZNF444	ENST00000587236.1 linkuse as main transcript	n.4807C>T		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

AF:

0.000440

AC:

AN:

152142

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

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:

0.000189

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000897

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000395

AC:

AN:

81018

Hom.:

AF XY:

0.000325

AC XY:

AN XY:

46138

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000201

Gnomad NFE exome

AF:

0.000992

Gnomad OTH exome

AF:

0.000402

GnomAD4 exome

AF:

0.000679

AC:

903

AN:

1330302

Hom.:

Cov.:

AF XY:

0.000663

AC XY:

434

AN XY:

654728

show subpopulations

Gnomad4 AFR exome

AF:

0.000263

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000880

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000179

Gnomad4 NFE exome

AF:

0.000801

Gnomad4 OTH exome

AF:

0.000760

GnomAD4 genome

AF:

0.000440

AC:

AN:

152254

Hom.:

Cov.:

AF XY:

0.000376

AC XY:

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.0000962

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000189

Gnomad4 NFE

AF:

0.000897

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000805

Hom.:

Bravo

AF:

0.000382

ExAC

AF:

0.000126

AC:

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

Oct 12, 2021

The c.911C>T (p.A304V) alteration is located in exon 5 (coding exon 3) of the ZNF444 gene. This alteration results from a C to T substitution at nucleotide position 911, causing the alanine (A) at amino acid position 304 to be replaced by a valine (V). 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

0.14

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.013

T;.

Eigen

Benign

-0.98

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.030

LIST_S2

Benign

0.45

T;T

M_CAP

Benign

0.035

MetaRNN

Benign

0.035

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.69

N;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

-0.95

N;.

REVEL

Benign

0.014

Sift

Benign

0.16

T;.

Sift4G

Benign

0.17

T;T

Polyphen

0.0090

B;B

Vest4

0.10

MVP

0.33

MPC

0.83

ClinPred

0.014

GERP RS

0.55

Varity_R

0.046

gMVP

0.12

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