1-23362925-G-C

Position:

• chr1-23362925-G-C

Variant summary

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

The NM_001077195.2(ZNF436):​c.457C>G​(p.Leu153Val) variant causes a missense change involving the alteration of a non-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)
• Consequence: ZNF436 NM_001077195.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.12

Genes affected

ZNF436 (HGNC:20814): (zinc finger protein 436) Predicted to enable DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Predicted to be involved in negative regulation of transcription by RNA polymerase II. Located in cytosol and nucleoplasm. [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
ZNF436	NM_001077195.2	c.457C>G	p.Leu153Val	missense_variant	4/4	ENST00000314011.9	NP_001070663.1
ZNF436	NM_030634.3	c.457C>G	p.Leu153Val	missense_variant	3/3		NP_085137.1
ZNF436	NM_001370652.1	c.403C>G	p.Leu135Val	missense_variant	3/3		NP_001357581.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF436	ENST00000314011.9	c.457C>G	p.Leu153Val	missense_variant	4/4	1	NM_001077195.2	ENSP00000313582.4
ZNF436	ENST00000374608.3	c.457C>G	p.Leu153Val	missense_variant	3/3	1		ENSP00000363736.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 33

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

Aug 02, 2022

The c.457C>G (p.L153V) alteration is located in exon 4 (coding exon 3) of the ZNF436 gene. This alteration results from a C to G substitution at nucleotide position 457, causing the leucine (L) at amino acid position 153 to be replaced by a valine (V). 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	0.080	D
BayesDel_noAF	Benign	-0.12
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T;T
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Benign	0.11	N
M_CAP	Benign	0.014	T
MetaRNN	Uncertain	0.53	D;D
MetaSVM	Benign	-0.47	T
MutationAssessor	Uncertain	2.5	M;M
PrimateAI	Uncertain	0.71	T
PROVEAN	Uncertain	-2.8	D;D
REVEL	Uncertain	0.29
Sift	Uncertain	0.0020	D;D
Sift4G	Uncertain	0.023	D;D
Polyphen		0.65	P;P
Vest4		0.37
MutPred		0.78		Gain of methylation at K158 (P = 0.0776);Gain of methylation at K158 (P = 0.0776);
MVP		0.70
MPC		0.76
ClinPred		0.98	D
GERP RS		5.1
Varity_R		0.54
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-23689418;