12-133011162-G-A

Position:

• chr12-133011162-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_019591.4(ZNF26):​c.1283G>A​(p.Cys428Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF26 NM_019591.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.40

Genes affected

ZNF26 (HGNC:13053): (zinc finger protein 26) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.931

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF26	NM_019591.4	c.1283G>A	p.Cys428Tyr	missense_variant	4/4	ENST00000328654.10	NP_062537.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF26	ENST00000328654.10	c.1283G>A	p.Cys428Tyr	missense_variant	4/4	1	NM_019591.4	ENSP00000333725	P1
ZNF26	ENST00000534834.1	n.3888G>A		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

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

Nov 08, 2021

The c.1283G>A (p.C428Y) alteration is located in exon 4 (coding exon 4) of the ZNF26 gene. This alteration results from a G to A substitution at nucleotide position 1283, causing the cysteine (C) at amino acid position 428 to be replaced by a tyrosine (Y). 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	Pathogenic	0.95
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.15
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.54	D;D
Eigen	Pathogenic	0.83
Eigen_PC	Pathogenic	0.70
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.71	T;T
M_CAP	Pathogenic	0.70	D
MetaRNN	Pathogenic	0.93	D;D
MetaSVM	Pathogenic	0.95	D
MutationAssessor	Pathogenic	3.8	H;.
MutationTaster	Benign	0.99	D;D
PrimateAI	Pathogenic	0.90	D
PROVEAN	Pathogenic	-11	D;D
REVEL	Uncertain	0.59
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;.
Vest4		0.61
MutPred		0.75		Gain of phosphorylation at C428 (P = 0.0851);.;
MVP		0.65
ClinPred		1.0	D
GERP RS		3.9
Varity_R		0.38
gMVP		0.31

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: chr12-133587748;