19-20624572-G-T

Position:

• chr19-20624572-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001076675.3(ZNF626):​c.1305C>A​(p.Asn435Lys) 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. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: ZNF626 NM_001076675.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -4.46

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]

ENSG00000269110 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.034661412).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF626	NM_001076675.3	c.1305C>A	p.Asn435Lys	missense_variant	4/4	ENST00000601440.6	NP_001070143.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF626	ENST00000601440.6	c.1305C>A	p.Asn435Lys	missense_variant	4/4	4	NM_001076675.3	ENSP00000469958.1
ENSG00000269110	ENST00000595094.1	n.363+21112C>A		intron_variant		5

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 45

GnomAD4 genome Cov.: 23

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 23, 2022

The c.1305C>A (p.N435K) alteration is located in exon 4 (coding exon 4) of the ZNF626 gene. This alteration results from a C to A substitution at nucleotide position 1305, causing the asparagine (N) at amino acid position 435 to be replaced by a lysine (K). 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	Benign	0.32
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.15
DANN	Benign	0.16
DEOGEN2	Benign	0.037	T;.
Eigen	Benign	-2.1
Eigen_PC	Benign	-2.1
FATHMM_MKL	Benign	0.0055	N
LIST_S2	Benign	0.0087	T;T
M_CAP	Benign	0.00056	T
MetaRNN	Benign	0.035	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.99	N;.
Sift4G	Benign	0.30	T;T
Polyphen		0.0010	B;.
Vest4		0.048
MutPred		0.37		Gain of methylation at N435 (P = 0.0022);Gain of methylation at N435 (P = 0.0022);
MVP		0.10
MPC		0.048
ClinPred		0.049	T
GERP RS		-0.26
Varity_R		0.075
gMVP		0.0046

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: rs879976867; hg19: chr19-20807378;