19-20624438-G-T

Position:

• chr19-20624438-G-T

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4

The NM_001076675.3(ZNF626):​c.1439C>A​(p.Pro480His) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 8)
  • Exomes 𝑓: 0.000043 (9 hom.)
  • Failed GnomAD Quality Control
• Consequence: ZNF626 NM_001076675.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.42

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 -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.30635965).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF626	NM_001076675.3	c.1439C>A	p.Pro480His	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.1439C>A	p.Pro480His	missense_variant	4/4	4	NM_001076675.3	ENSP00000469958	P1

Frequencies

GnomAD3 genomes Cov.: 8

GnomAD3 exomes AF: 0.0000329 AC: 5 AN: 152206 Hom.: 0 AF XY: 0.0000122 AC XY: 1 AN XY: 81804

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000489

Gnomad ASJ exome AF: 0.000205

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000923

Gnomad NFE exome AF: 0.0000298

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000426 AC: 27 AN: 634056 Hom.: 9 Cov.: 9 AF XY: 0.0000399 AC XY: 13 AN XY: 325568

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000809

Gnomad4 ASJ exome AF: 0.000135

Gnomad4 EAS exome AF: 0.000183

Gnomad4 SAS exome AF: 0.0000568

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000283

Gnomad4 OTH exome AF: 0.0000996

GnomAD4 genome Cov.: 8

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

Aug 10, 2021

The c.1439C>A (p.P480H) 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 1439, causing the proline (P) at amino acid position 480 to be replaced by a histidine (H). 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	0.38
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	15
DANN	Benign	0.88
DEOGEN2	Benign	0.10	T
Eigen	Benign	-0.46
Eigen_PC	Benign	-0.80
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.021	T
M_CAP	Benign	0.0020	T
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-0.45	T
MutationAssessor	Pathogenic	2.9	M
MutationTaster	Benign	0.99	N
Sift4G	Uncertain	0.0030	D
Polyphen		1.0	D
Vest4		0.32
MutPred		0.40		Loss of catalytic residue at P480 (P = 0.0898);
MVP		0.48
MPC		0.21
ClinPred		0.36	T
GERP RS		-1.7
Varity_R		0.16
gMVP		0.028

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: rs1555769212; hg19: chr19-20807244;