19-20624438-G-T

Variant names:

• chr19-20624438-G-T
• rs1555769212
• NM_001076675.3:c.1439C>A

Variant summary

Our verdict is Likely benign. The variant received -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. 11/19 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. P480S) has been classified 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
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -1 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001076675.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF626	NM_001076675.3	MANE Select	c.1439C>A	p.Pro480His	missense	Exon 4 of 4	NP_001070143.1	Q68DY1-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF626	ENST00000601440.6	TSL:4 MANE Select	c.1439C>A	p.Pro480His	missense	Exon 4 of 4	ENSP00000469958.1	Q68DY1-1
	ENSG00000269110	ENST00000595094.1	TSL:5	n.363+21246C>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 8

GnomAD2 exomes AF: 0.0000329 AC: 5 AN: 152206 AF XY: 0.0000122

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 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

African (AFR) AF: 0.00 AC: 0 AN: 25024

American (AMR) AF: 0.0000809 AC: 2 AN: 24714

Ashkenazi Jewish (ASJ) AF: 0.000135 AC: 2 AN: 14800

East Asian (EAS) AF: 0.000183 AC: 5 AN: 27330

South Asian (SAS) AF: 0.0000568 AC: 3 AN: 52818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32660

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2510

European-Non Finnish (NFE) AF: 0.0000283 AC: 12 AN: 424070

Other (OTH) AF: 0.0000996 AC: 3 AN: 30130

GnomAD4 genome Cov.: 8

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		2.4
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
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs1555769212; hg19: chr19-20807244;