Variant 18-76880165-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000320610.14(ZNF236):c.1037C>T(p.Ser346Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00303 in 1,614,048 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0022 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0031 ( 9 hom. )

Consequence

ZNF236
ENST00000320610.14 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.56

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 Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006637037).

BP6

Variant 18-76880165-C-T is Benign according to our data. Variant chr18-76880165-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 710889.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr18-76880165-C-T is described in Lovd as [Likely_benign].

BS2

High AC in GnomAd4 at 334 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF236	NM_001306089.2 linkuse as main transcript	c.1037C>T	p.Ser346Leu	missense_variant	8/31	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.1037C>T	p.Ser346Leu	missense_variant	8/31	1	NM_001306089.2	ENSP00000322361	P1
ZNF236	ENST00000253159.12 linkuse as main transcript	c.1031C>T	p.Ser344Leu	missense_variant	8/31	1		ENSP00000253159		Q9UL36-1
ZNF236	ENST00000543926.6 linkuse as main transcript	c.1031C>T	p.Ser344Leu	missense_variant, NMD_transcript_variant	8/32	1		ENSP00000444524		Q9UL36-2
ZNF236	ENST00000579322.1 linkuse as main transcript	n.1309C>T		non_coding_transcript_exon_variant	7/8	2

Frequencies

GnomAD3 genomes

AF:

0.00220

AC:

335

AN:

152090

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000966

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00131

Gnomad ASJ

AF:

0.00346

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.00132

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00350

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00224

AC:

555

AN:

248272

Hom.:

AF XY:

0.00236

AC XY:

318

AN XY:

134876

show subpopulations

Gnomad AFR exome

AF:

0.000717

Gnomad AMR exome

AF:

0.000956

Gnomad ASJ exome

AF:

0.00308

Gnomad EAS exome

AF:

0.0000556

Gnomad SAS exome

AF:

0.00209

Gnomad FIN exome

AF:

0.00139

Gnomad NFE exome

AF:

0.00329

Gnomad OTH exome

AF:

0.00264

GnomAD4 exome

AF:

0.00312

AC:

4554

AN:

1461840

Hom.:

Cov.:

AF XY:

0.00316

AC XY:

2296

AN XY:

727224

show subpopulations

Gnomad4 AFR exome

AF:

0.000478

Gnomad4 AMR exome

AF:

0.000917

Gnomad4 ASJ exome

AF:

0.00348

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00223

Gnomad4 FIN exome

AF:

0.00124

Gnomad4 NFE exome

AF:

0.00358

Gnomad4 OTH exome

AF:

0.00247

GnomAD4 genome

AF:

0.00219

AC:

334

AN:

152208

Hom.:

Cov.:

AF XY:

0.00200

AC XY:

149

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.000963

Gnomad4 AMR

AF:

0.00131

Gnomad4 ASJ

AF:

0.00346

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.00132

Gnomad4 NFE

AF:

0.00350

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00277

Hom.:

Bravo

AF:

0.00206

TwinsUK

AF:

0.00243

AC:

ALSPAC

AF:

0.00337

AC:

ESP6500AA

AF:

0.00126

AC:

ESP6500EA

AF:

0.00420

AC:

ExAC

AF:

0.00213

AC:

258

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00338

EpiControl

AF:

0.00320

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jun 19, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.016

T;T;.

Eigen

Benign

-0.092

Eigen_PC

Benign

-0.15

FATHMM_MKL

Uncertain

0.89

LIST_S2

Uncertain

0.91

D;D;D

M_CAP

Benign

0.083

MetaRNN

Benign

0.0066

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.3

.;M;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.40

PROVEAN

Benign

-1.4

N;N;.

REVEL

Benign

0.13

Sift

Benign

0.072

T;T;.

Sift4G

Benign

0.68

T;T;T

Polyphen

0.52

.;P;.

Vest4

0.43

MVP

0.24

MPC

0.64

ClinPred

0.032

GERP RS

5.0

Varity_R

0.11

gMVP

0.43

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