12-133011315-A-G

Position:

• chr12-133011315-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_019591.4(ZNF26):​c.1436A>G​(p.Glu479Gly) 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. 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: 3.22

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26223958).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF26	NM_019591.4	c.1436A>G	p.Glu479Gly	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.1436A>G	p.Glu479Gly	missense_variant	4/4	1	NM_019591.4	ENSP00000333725	P1
ZNF26	ENST00000534834.1	n.4041A>G		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

Dec 21, 2022

The c.1436A>G (p.E479G) alteration is located in exon 4 (coding exon 4) of the ZNF26 gene. This alteration results from a A to G substitution at nucleotide position 1436, causing the glutamic acid (E) at amino acid position 479 to be replaced by a glycine (G). 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	0.38
BayesDel_addAF	Benign	-0.068	T
BayesDel_noAF	Benign	-0.34
CADD	Uncertain	25
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.091	T;T
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.75	T;T
M_CAP	Benign	0.037	D
MetaRNN	Benign	0.26	T;T
MetaSVM	Benign	-0.77	T
MutationAssessor	Benign	1.8	L;.
MutationTaster	Benign	0.56	N;N
PrimateAI	Uncertain	0.61	T
PROVEAN	Pathogenic	-6.2	D;D
REVEL	Benign	0.13
Sift	Uncertain	0.012	D;D
Sift4G	Pathogenic	0.0010	D;D
Polyphen		1.0	D;.
Vest4		0.40
MutPred		0.37		Loss of solvent accessibility (P = 0.0187);.;
MVP		0.21
ClinPred		0.95	D
GERP RS		3.9
Varity_R		0.23
gMVP		0.034

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: chr12-133587901;