Variant 18-76875567-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The ENST00000320610.14(ZNF236):c.743A>G(p.Lys248Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000106 in 1,605,986 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

ZNF236
ENST00000320610.14 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.61

Variant links:

Genes affected

ZNF236 (HGNC:13028): (zinc finger protein 236) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Involved in cellular response to glucose stimulus. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF236 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.1479525).

BS2

High AC in GnomAdExome4 at 15 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF236	NM_001306089.2 linkuse as main transcript	c.743A>G	p.Lys248Arg	missense_variant	6/31	ENST00000320610.14	NP_001293018.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF236	ENST00000320610.14 linkuse as main transcript	c.743A>G	p.Lys248Arg	missense_variant	6/31	1	NM_001306089.2	ENSP00000322361	P1
ZNF236	ENST00000253159.12 linkuse as main transcript	c.737A>G	p.Lys246Arg	missense_variant	6/31	1		ENSP00000253159		Q9UL36-1
ZNF236	ENST00000543926.6 linkuse as main transcript	c.737A>G	p.Lys246Arg	missense_variant, NMD_transcript_variant	6/32	1		ENSP00000444524		Q9UL36-2
ZNF236	ENST00000579322.1 linkuse as main transcript	n.1015A>G		non_coding_transcript_exon_variant	5/8	2

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000410

AC:

AN:

244106

Hom.:

AF XY:

0.00

AC XY:

AN XY:

132406

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:

0.0000344

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000103

AC:

AN:

1453778

Hom.:

Cov.:

AF XY:

0.00000415

AC XY:

AN XY:

722672

show subpopulations

Gnomad4 AFR exome

AF:

0.0000300

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000236

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000993

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152208

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

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

Jan 05, 2022

The c.737A>G (p.K246R) alteration is located in exon 6 (coding exon 6) of the ZNF236 gene. This alteration results from a A to G substitution at nucleotide position 737, causing the lysine (K) at amino acid position 246 to be replaced by an arginine (R). 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

0.19

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Benign

0.90

DEOGEN2

Benign

0.012

T;T;.

Eigen

Benign

-0.67

Eigen_PC

Benign

-0.49

FATHMM_MKL

Uncertain

0.78

LIST_S2

Uncertain

0.88

D;D;D

M_CAP

Benign

0.0093

MetaRNN

Benign

0.15

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.26

.;N;.

MutationTaster

Benign

0.63

D;N

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

-0.83

.;N;.

REVEL

Benign

0.059

Sift

Benign

0.32

.;T;.

Sift4G

Benign

0.19

T;T;T

Polyphen

0.051

.;B;.

Vest4

0.12

MutPred

0.40

.;Loss of ubiquitination at K246 (P = 0.0218);Loss of ubiquitination at K246 (P = 0.0218);

MVP

0.40

MPC

0.58

ClinPred

0.099

GERP RS

3.4

Varity_R

0.11

gMVP

0.24

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