Genetic Variant ZNF44:p.His443Tyr (chr19-12272928-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_016264.4(ZNF44):c.1327C>T(p.His443Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00144 in 1,614,094 control chromosomes in the GnomAD database, including 32 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0078 ( 17 hom., cov: 33)

Exomes 𝑓: 0.00078 ( 15 hom. )

Consequence

ZNF44
NM_016264.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 3.33

Variant links:

Genes affected

ZNF44 (HGNC:13110): (zinc finger protein 44) 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]

ZNF44 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=0.0073007345).

BP6

Variant 19-12272928-G-A is Benign according to our data. Variant chr19-12272928-G-A is described in ClinVar as [Benign]. Clinvar id is 777291.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0078 (1187/152242) while in subpopulation AFR AF= 0.0275 (1144/41542). AF 95% confidence interval is 0.0262. There are 17 homozygotes in gnomad4. There are 591 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 17 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF44	NM_016264.4 link	c.1327C>T	p.His443Tyr	missense_variant	Exon 4 of 4	ENST00000355684.6	NP_057348.3	F8W7T7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF44	ENST00000355684.6 link	c.1327C>T	p.His443Tyr	missense_variant	Exon 4 of 4	2	NM_016264.4	ENSP00000347910.5		F8W7T7

Frequencies

GnomAD3 genomes

AF:

0.00776

AC:

1181

AN:

152124

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0275

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00209

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00430

GnomAD3 exomes

AF:

0.00191

AC:

478

AN:

250268

Hom.:

AF XY:

0.00143

AC XY:

194

AN XY:

135678

show subpopulations

Gnomad AFR exome

AF:

0.0281

Gnomad AMR exome

AF:

0.00101

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000882

Gnomad OTH exome

AF:

0.000329

GnomAD4 exome

AF:

0.000781

AC:

1141

AN:

1461852

Hom.:

Cov.:

AF XY:

0.000663

AC XY:

482

AN XY:

727212

show subpopulations

Gnomad4 AFR exome

AF:

0.0280

Gnomad4 AMR exome

AF:

0.00127

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000189

Gnomad4 OTH exome

AF:

0.00195

GnomAD4 genome

AF:

0.00780

AC:

1187

AN:

152242

Hom.:

Cov.:

AF XY:

0.00794

AC XY:

591

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.0275

Gnomad4 AMR

AF:

0.00209

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00425

Alfa

AF:

0.00118

Hom.:

Bravo

AF:

0.00871

ESP6500AA

AF:

0.0248

AC:

109

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00243

AC:

295

Asia WGS

AF:

0.00202

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.68

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.22

T;.

Eigen

Benign

0.19

Eigen_PC

Benign

-0.12

FATHMM_MKL

Benign

0.0018

LIST_S2

Uncertain

0.89

D;D

MetaRNN

Benign

0.0073

T;T

MetaSVM

Uncertain

-0.19

MutationAssessor

Pathogenic

3.1

M;.

PrimateAI

Benign

0.48

PROVEAN

Pathogenic

-5.3

D;D

REVEL

Uncertain

0.31

Sift

Uncertain

0.0010

D;D

Sift4G

Uncertain

0.0040

D;D

Polyphen

1.0

D;D

Vest4

0.19

MVP

0.69

MPC

0.39

ClinPred

0.063

GERP RS

1.0

Varity_R

0.45

gMVP

0.055

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