NM_001032373.2:c.19G>A

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001032373.2(ZNF226):c.19G>A(p.Ala7Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000745 in 1,611,218 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

ZNF226
NM_001032373.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.601

Publications

0 publications found

Variant links:

Genes affected

ZNF226 (HGNC:13019): (zinc finger protein 226) Predicted to enable DNA-binding transcription activator activity, RNA polymerase II-specific and RNA polymerase II cis-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]

ZNF226 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.057491302).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF226	NM_001032373.2 link	c.19G>A	p.Ala7Thr	missense_variant	Exon 4 of 6	ENST00000337433.10	NP_001027545.1	Q9NYT6-1A0A024R0P4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF226	ENST00000337433.10 link	c.19G>A	p.Ala7Thr	missense_variant	Exon 4 of 6	1	NM_001032373.2	ENSP00000336719.5		Q9NYT6-1

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000771

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000278

AC:

AN:

251360

AF XY:

0.0000221

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000326

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000548

AC:

AN:

1459000

Hom.:

Cov.:

AF XY:

0.00000551

AC XY:

AN XY:

725808

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33396

American (AMR)

AF:

0.00

AC:

AN:

44610

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26060

East Asian (EAS)

AF:

0.000152

AC:

AN:

39564

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86238

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52996

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5750

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1110164

Other (OTH)

AF:

0.0000166

AC:

AN:

60222

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152218

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74370

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41460

American (AMR)

AF:

0.00

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000771

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68036

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.588

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000329

Hom.:

Bravo

AF:

0.0000227

ExAC

AF:

0.0000247

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Sep 01, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.19G>A (p.A7T) alteration is located in exon 4 (coding exon 2) of the ZNF226 gene. This alteration results from a G to A substitution at nucleotide position 19, causing the alanine (A) at amino acid position 7 to be replaced by a threonine (T). 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

0.087

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.79

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.028

.;.;T;.;.;.;.;.;.;.;.;.;.;.;T;T;.

Eigen

Benign

-0.70

Eigen_PC

Benign

-0.71

FATHMM_MKL

Benign

0.052

LIST_S2

Benign

0.33

T;.;T;T;T;T;.;.;.;T;D;T;T;T;.;.;T

M_CAP

Benign

0.0050

MetaRNN

Benign

0.057

T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

1.3

.;.;L;.;.;.;.;L;L;L;.;.;.;.;L;L;.

PhyloP100

-0.60

PrimateAI

Benign

0.35

PROVEAN

Benign

-1.3

.;.;N;.;.;.;.;D;.;D;.;.;.;.;.;N;.

REVEL

Benign

0.033

Sift

Benign

0.23

.;.;T;.;.;.;.;T;.;T;.;.;.;.;.;T;.

Sift4G

Benign

0.13

T;T;T;T;T;T;T;T;T;T;D;T;T;T;T;T;T

Polyphen

0.025

.;.;B;.;.;.;.;.;.;.;.;.;.;.;B;B;.

Vest4

0.15, 0.15, 0.14, 0.16

MutPred

0.34

Gain of phosphorylation at A7 (P = 0.085);Gain of phosphorylation at A7 (P = 0.085);Gain of phosphorylation at A7 (P = 0.085);Gain of phosphorylation at A7 (P = 0.085);Gain of phosphorylation at A7 (P = 0.085);Gain of phosphorylation at A7 (P = 0.085);Gain of phosphorylation at A7 (P = 0.085);Gain of phosphorylation at A7 (P = 0.085);Gain of phosphorylation at A7 (P = 0.085);Gain of phosphorylation at A7 (P = 0.085);Gain of phosphorylation at A7 (P = 0.085);Gain of phosphorylation at A7 (P = 0.085);Gain of phosphorylation at A7 (P = 0.085);Gain of phosphorylation at A7 (P = 0.085);Gain of phosphorylation at A7 (P = 0.085);Gain of phosphorylation at A7 (P = 0.085);Gain of phosphorylation at A7 (P = 0.085);

MVP

0.37

MPC

0.019

ClinPred

0.037

GERP RS

0.92

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.020

gMVP

0.043

Mutation Taster

=89/11

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.18

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

NM_001032373.2:c.19G>A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over