Variant 18-76878106-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001306089.2(ZNF236):c.938G>A(p.Gly313Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,460,910 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

ZNF236
NM_001306089.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.42

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.20642212).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF236	NM_001306089.2 linkuse as main transcript	c.938G>A	p.Gly313Glu	missense_variant	7/31	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.938G>A	p.Gly313Glu	missense_variant	7/31	1	NM_001306089.2	ENSP00000322361	P1
ZNF236	ENST00000253159.12 linkuse as main transcript	c.932G>A	p.Gly311Glu	missense_variant	7/31	1		ENSP00000253159		Q9UL36-1
ZNF236	ENST00000543926.6 linkuse as main transcript	c.932G>A	p.Gly311Glu	missense_variant, NMD_transcript_variant	7/32	1		ENSP00000444524		Q9UL36-2
ZNF236	ENST00000579322.1 linkuse as main transcript	n.1210G>A		non_coding_transcript_exon_variant	6/8	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000401

AC:

AN:

249402

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135316

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:

0.00

Gnomad NFE exome

AF:

0.00000883

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1460910

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726770

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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

Mar 29, 2023

The c.932G>A (p.G311E) alteration is located in exon 7 (coding exon 7) of the ZNF236 gene. This alteration results from a G to A substitution at nucleotide position 932, causing the glycine (G) at amino acid position 311 to be replaced by a glutamic acid (E). 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

0.28

BayesDel_addAF

Uncertain

0.16

BayesDel_noAF

Uncertain

-0.010

CADD

Benign

DANN

Benign

0.48

DEOGEN2

Benign

0.0019

T;T;.

Eigen

Benign

-0.047

Eigen_PC

Benign

0.0053

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.90

D;D;D

M_CAP

Benign

0.016

MetaRNN

Benign

0.21

T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Uncertain

2.3

.;M;.

MutationTaster

Benign

0.98

N;N

PrimateAI

Uncertain

0.60

PROVEAN

Benign

1.5

.;N;.

REVEL

Benign

0.23

Sift

Benign

0.76

.;T;.

Sift4G

Benign

0.56

T;T;T

Polyphen

0.96

.;D;.

Vest4

0.42

MutPred

0.28

.;Gain of loop (P = 0.1081);Gain of loop (P = 0.1081);

MVP

0.75

MPC

1.4

ClinPred

0.65

GERP RS

5.1

Varity_R

0.13

gMVP

0.25

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