19-20624441-C-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001076675.3(ZNF626):c.1436G>C(p.Arg479Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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: 6)
  • Exomes 𝑓: 0.000063 (11 hom.)
  • Failed GnomAD Quality Control
• Consequence: ZNF626 NM_001076675.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0870

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 Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.044294685).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF626	NM_001076675.3	c.1436G>C	p.Arg479Thr	missense_variant	4/4	ENST00000601440.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF626	ENST00000601440.6	c.1436G>C	p.Arg479Thr	missense_variant	4/4	4	NM_001076675.3	P1

Frequencies

GnomAD3 genomes Cov.: 6

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000626 AC: 31 AN: 495080 Hom.: 11 Cov.: 8 AF XY: 0.0000631 AC XY: 16 AN XY: 253726

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.000396

Gnomad4 EAS exome AF: 0.000211

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.000163

Gnomad4 NFE exome AF: 0.0000414

Gnomad4 OTH exome AF: 0.000228

GnomAD4 genome Cov.: 6

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

Sep 17, 2021

The c.1436G>C (p.R479T) alteration is located in exon 4 (coding exon 4) of the ZNF626 gene. This alteration results from a G to C substitution at nucleotide position 1436, causing the arginine (R) at amino acid position 479 to be replaced by a threonine (T). 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	0.29
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.72
Cadd	Benign	11
Dann	Benign	0.52
DEOGEN2	Benign	0.039	T
Eigen	Benign	-2.1
Eigen_PC	Benign	-2.2
FATHMM_MKL	Benign	0.062	N
LIST_S2	Benign	0.035	T
M_CAP	Benign	0.0028	T
MetaRNN	Benign	0.044	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L
MutationTaster	Benign	1.0	N
Sift4G	Uncertain	0.0020	D
Polyphen		0.0040	B
Vest4		0.16
MutPred		0.39		Gain of ubiquitination at K482 (P = 0.0516);
MVP		0.23
MPC		0.059
ClinPred		0.031	T
GERP RS		-1.7
Varity_R		0.072
gMVP		0.011

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: chr19-20807247;