18-76878093-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001306089.2(ZNF236):​c.925A>T​(p.Met309Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,613,346 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

ZNF236
NM_001306089.2 missense

Scores

2
4
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.08
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.29111445).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ZNF236NM_001306089.2 linkuse as main transcriptc.925A>T p.Met309Leu missense_variant 7/31 ENST00000320610.14 NP_001293018.1 Q9UL36J9JID5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ZNF236ENST00000320610.14 linkuse as main transcriptc.925A>T p.Met309Leu missense_variant 7/311 NM_001306089.2 ENSP00000322361.9 J9JID5
ZNF236ENST00000253159.12 linkuse as main transcriptc.919A>T p.Met307Leu missense_variant 7/311 ENSP00000253159.8 Q9UL36-1
ZNF236ENST00000543926.6 linkuse as main transcriptn.919A>T non_coding_transcript_exon_variant 7/321 ENSP00000444524.2 Q9UL36-2
ZNF236ENST00000579322.1 linkuse as main transcriptn.1197A>T non_coding_transcript_exon_variant 6/82

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152234
Hom.:
0
Cov.:
33
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:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000205
AC:
3
AN:
1461112
Hom.:
0
Cov.:
30
AF XY:
0.00000413
AC XY:
3
AN XY:
726900
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:
0.00000270
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152234
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
74374
show subpopulations
Gnomad4 AFR
AF:
0.00
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:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000756

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 submitterclinical testingAmbry GeneticsDec 04, 2024The c.919A>T (p.M307L) alteration is located in exon 7 (coding exon 7) of the ZNF236 gene. This alteration results from a A to T substitution at nucleotide position 919, causing the methionine (M) at amino acid position 307 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
Uncertain
0.45
BayesDel_addAF
Uncertain
0.020
T
BayesDel_noAF
Benign
-0.21
CADD
Uncertain
24
DANN
Benign
0.95
DEOGEN2
Benign
0.00096
T;T;.
Eigen
Benign
0.17
Eigen_PC
Uncertain
0.31
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Benign
0.85
T;T;T
M_CAP
Benign
0.025
D
MetaRNN
Benign
0.29
T;T;T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
0.41
.;N;.
PrimateAI
Pathogenic
0.79
T
PROVEAN
Benign
-0.46
N;N;.
REVEL
Uncertain
0.34
Sift
Benign
0.41
T;T;.
Sift4G
Benign
0.13
T;T;T
Polyphen
0.93
.;P;.
Vest4
0.51
MutPred
0.37
.;Gain of methylation at K306 (P = 0.033);Gain of methylation at K306 (P = 0.033);
MVP
0.52
MPC
1.6
ClinPred
0.88
D
GERP RS
5.1
Varity_R
0.26
gMVP
0.29

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.

Other links and lift over

dbSNP: rs1053283924; hg19: chr18-74590049; API