18-76880152-G-C

Position:

• chr18-76880152-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001306089.2(ZNF236):​c.1024G>C​(p.Ala342Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF236 NM_001306089.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.973

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 (HGNC:):

ACMG classification

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=0.046099454).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF236	NM_001306089.2	c.1024G>C	p.Ala342Pro	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	c.1024G>C	p.Ala342Pro	missense_variant	8/31	1	NM_001306089.2	ENSP00000322361.9
ZNF236	ENST00000253159.12	c.1018G>C	p.Ala340Pro	missense_variant	8/31	1		ENSP00000253159.8
ZNF236	ENST00000543926.6	n.1018G>C		non_coding_transcript_exon_variant	8/32	1		ENSP00000444524.2
ZNF236	ENST00000579322.1	n.1296G>C		non_coding_transcript_exon_variant	7/8	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 15, 2024

The c.1018G>C (p.A340P) alteration is located in exon 8 (coding exon 8) of the ZNF236 gene. This alteration results from a G to C substitution at nucleotide position 1018, causing the alanine (A) at amino acid position 340 to be replaced by a proline (P). 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	0.077
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	14
DANN	Uncertain	0.98
DEOGEN2	Benign	0.014	T;T;.
Eigen	Benign	-0.77
Eigen_PC	Benign	-0.69
FATHMM_MKL	Benign	0.36	N
LIST_S2	Benign	0.75	T;T;T
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.046	T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.76	.;N;.
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.90	N;N;.
REVEL	Benign	0.043
Sift	Benign	0.14	T;T;.
Sift4G	Benign	0.29	T;T;T
Polyphen		0.0	.;B;.
Vest4		0.12
MutPred		0.40		.;Gain of glycosylation at A340 (P = 0.0458);Gain of glycosylation at A340 (P = 0.0458);
MVP		0.18
MPC		0.82
ClinPred		0.066	T
GERP RS		0.61
Varity_R		0.11
gMVP		0.44

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr18-74592108;