19-20625171-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001076675.3(ZNF626):c.706A>G(p.Lys236Glu) 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: ZNF626 NM_001076675.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.57

Genes affected

ZNF626 (HGNC:30461): (zinc finger protein 626) 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, DNA-templated. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31831074).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF626	NM_001076675.3	c.706A>G	p.Lys236Glu	missense_variant	4/4	ENST00000601440.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF626	ENST00000601440.6	c.706A>G	p.Lys236Glu	missense_variant	4/4	4	NM_001076675.3	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 82

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

Mar 01, 2023

The c.706A>G (p.K236E) alteration is located in exon 4 (coding exon 4) of the ZNF626 gene. This alteration results from a A to G substitution at nucleotide position 706, causing the lysine (K) at amino acid position 236 to be replaced by a glutamic acid (E). 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	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
Cadd	Benign	19
Dann	Uncertain	1.0
DEOGEN2	Benign	0.046	T;.
Eigen	Benign	0.036
Eigen_PC	Benign	-0.19
FATHMM_MKL	Benign	0.49	N
LIST_S2	Benign	0.036	T;T
M_CAP	Benign	0.0016	T
MetaRNN	Benign	0.32	T;T
MetaSVM	Benign	-0.58	T
MutationAssessor	Uncertain	2.5	M;.
MutationTaster	Benign	1.0	N
Sift4G	Uncertain	0.0040	D;D
Polyphen		0.99	D;.
Vest4		0.18
MutPred		0.47		Loss of methylation at K236 (P = 8e-04);Loss of methylation at K236 (P = 8e-04);
MVP		0.56
MPC		0.34
ClinPred		0.86	D
GERP RS		0.80
Varity_R		0.39
gMVP		0.0093

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

LitVar

Other links and lift over

dbSNP: rs1969811524; hg19: chr19-20807977;