19-20625249-A-G

Variant summary

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

The NM_001076675.3(ZNF626):c.628T>C(p.Phe210Leu) variant causes a missense change. 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: ZNF626 NM_001076675.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.26

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF626	NM_001076675.3	c.628T>C	p.Phe210Leu	missense_variant	4/4	ENST00000601440.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF626	ENST00000601440.6	c.628T>C	p.Phe210Leu	missense_variant	4/4	4	NM_001076675.3	P1
ZNF626	ENST00000595405.1	c.400T>C	p.Phe134Leu	missense_variant	2/2	3

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

Nov 09, 2021

The c.628T>C (p.F210L) alteration is located in exon 4 (coding exon 4) of the ZNF626 gene. This alteration results from a T to C substitution at nucleotide position 628, causing the phenylalanine (F) at amino acid position 210 to be replaced by a leucine (L). 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	Benign	-0.19	T
BayesDel_noAF	Benign	-0.52
Cadd	Benign	18
Dann	Benign	0.88
DEOGEN2	Benign	0.12	T;.;.
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.77
FATHMM_MKL	Benign	0.46	N
LIST_S2	Benign	0.51	T;T;D
M_CAP	Benign	0.0027	T
MetaRNN	Uncertain	0.57	D;D;D
MetaSVM	Benign	-0.76	T
MutationAssessor	Uncertain	2.1	M;.;.
MutationTaster	Benign	1.0	N
Sift4G	Uncertain	0.0090	D;D;D
Polyphen		0.14	B;.;.
Vest4		0.22
MutPred		0.71		Gain of MoRF binding (P = 0.1328);Gain of MoRF binding (P = 0.1328);.;
MVP		0.57
MPC		0.31
ClinPred		0.68	D
GERP RS		0.80
Varity_R		0.28
gMVP		0.018

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: chr19-20808055;