19-20624439-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001076675.3(ZNF626):c.1438C>T(p.Pro480Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P480H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 7)
  • Exomes 𝑓: 0.0000032 (1 hom.)
  • Failed GnomAD Quality Control
• Consequence: ZNF626 NM_001076675.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.80

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 -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.15873972).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF626	NM_001076675.3	c.1438C>T	p.Pro480Ser	missense_variant	4/4	ENST00000601440.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF626	ENST00000601440.6	c.1438C>T	p.Pro480Ser	missense_variant	4/4	4	NM_001076675.3	P1

Frequencies

GnomAD3 genomes Cov.: 7

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000320 AC: 2 AN: 624488 Hom.: 1 Cov.: 8 AF XY: 0.00000623 AC XY: 2 AN XY: 320780

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000478

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 7

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

Jul 20, 2021

The c.1438C>T (p.P480S) alteration is located in exon 4 (coding exon 4) of the ZNF626 gene. This alteration results from a C to T substitution at nucleotide position 1438, causing the proline (P) at amino acid position 480 to be replaced by a serine (S). 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	-0.34	T
BayesDel_noAF	Benign	-0.73
Cadd	Benign	14
Dann	Benign	0.65
DEOGEN2	Benign	0.057	T
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.64
FATHMM_MKL	Benign	0.60	D
LIST_S2	Benign	0.029	T
M_CAP	Benign	0.0021	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.79	T
MutationAssessor	Benign	1.3	L
MutationTaster	Benign	0.99	N
Sift4G	Uncertain	0.020	D
Polyphen		0.34	B
Vest4		0.21
MutPred		0.42		Gain of phosphorylation at P480 (P = 0.0728);
MVP		0.50
MPC		0.10
ClinPred		0.37	T
GERP RS		0.83
Varity_R		0.044
gMVP		0.019

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: chr19-20807245;