18-76875524-A-G

Position:

• chr18-76875524-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000320610.14(ZNF236):​c.700A>G​(p.Lys234Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ZNF236 ENST00000320610.14 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.99

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF236	NM_001306089.2	c.700A>G	p.Lys234Glu	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	c.700A>G	p.Lys234Glu	missense_variant	6/31	1	NM_001306089.2	ENSP00000322361	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1406826 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 696038

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Cerebellar ataxia;C0029124:Optic atrophy;C0454644:Delayed speech and language development;C0557874:Global developmental delay Uncertain:1

Uncertain significance, criteria provided, single submitter

research

HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology

May 04, 2020

ACMG codes: PM2, PP3 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.096	T;T;.
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.72	T;T;T
M_CAP	Benign	0.042	D
MetaRNN	Uncertain	0.70	D;D;D
MetaSVM	Benign	-1.2	T
MutationAssessor	Uncertain	2.4	.;M;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Pathogenic	0.89	D
PROVEAN	Uncertain	-3.2	.;D;.
REVEL	Uncertain	0.36
Sift	Uncertain	0.0070	.;D;.
Sift4G	Uncertain	0.016	D;D;D
Polyphen		1.0	.;D;.
Vest4		0.53
MutPred		0.53		.;Loss of methylation at K232 (P = 0.0075);Loss of methylation at K232 (P = 0.0075);
MVP		0.44
MPC		1.4
ClinPred		0.98	D
GERP RS		6.0
Varity_R		0.63
gMVP		0.79

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: chr18-74587480;