Variant 19-44175878-A-C 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_001032373.2(ZNF226):c.616A>C(p.Ile206Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000136 in 1,612,990 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 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

ZNF226
NM_001032373.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.58

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 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=0.021626472).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF226	NM_001032373.2 link	c.616A>C	p.Ile206Leu	missense_variant	6/6	ENST00000337433.10	NP_001027545.1	Q9NYT6-1A0A024R0P4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZNF226	ENST00000337433.10 link	c.616A>C	p.Ile206Leu	missense_variant	6/6	1	NM_001032373.2	ENSP00000336719.5	Q9NYT6-1
ZNF226	ENST00000454662.6 link	c.616A>C	p.Ile206Leu	missense_variant	6/6	1		ENSP00000393265.1	Q9NYT6-1
ZNF226	ENST00000590089.5 link	c.616A>C	p.Ile206Leu	missense_variant	7/7	1		ENSP00000465121.1	Q9NYT6-1
ZNF226	ENST00000588883.5 link	c.*2891A>C		3_prime_UTR_variant	5/5	1		ENSP00000465401.1	K7EK05

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152168

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:

0.000962

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

GnomAD3 exomes

AF:

0.0000767

AC:

AN:

247714

Hom.:

AF XY:

0.0000447

AC XY:

AN XY:

134362

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00106

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:

0.0000116

AC:

AN:

1460822

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

726630

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000403

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152168

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000962

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000255

Hom.:

Bravo

AF:

0.0000340

ExAC

AF:

0.0000910

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

Jun 29, 2023

The c.616A>C (p.I206L) alteration is located in exon 6 (coding exon 4) of the ZNF226 gene. This alteration results from a A to C substitution at nucleotide position 616, causing the isoleucine (I) at amino acid position 206 to be replaced by a leucine (L). 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

0.072

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.37

DANN

Benign

0.86

DEOGEN2

Benign

0.0030

T;T;T

Eigen

Benign

-0.99

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.079

LIST_S2

Benign

0.19

T;.;.

M_CAP

Benign

0.0014

MetaRNN

Benign

0.022

T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.84

L;L;L

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.38

N;.;N

REVEL

Benign

0.057

Sift

Benign

0.62

T;.;T

Sift4G

Benign

0.72

T;T;T

Polyphen

0.0030

B;B;B

Vest4

0.14

MutPred

0.49

Loss of methylation at K201 (P = 0.0527);Loss of methylation at K201 (P = 0.0527);Loss of methylation at K201 (P = 0.0527);

MVP

0.24

MPC

0.018

ClinPred

0.066

GERP RS

1.6

Varity_R

0.033

gMVP

0.023

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