19-20624738-C-T

Variant names:

• chr19-20624738-C-T
• rs782512962
• NM_001076675.3:c.1139G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001076675.3(ZNF626):​c.1139G>A​(p.Arg380Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000211 in 132,768 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00021 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000028 (1 hom.)
  • Failed GnomAD Quality Control
• Consequence: ZNF626 NM_001076675.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -3.02
• 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.025245398).

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.1139G>A	p.Arg380Gln	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.1139G>A	p.Arg380Gln	missense	Exon 4 of 4	ENSP00000469958.1	Q68DY1-1
	ENSG00000269110	ENST00000595094.1	TSL:5	n.363+20946G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000211 AC: 28 AN: 132768 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000580

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000295

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000163

Gnomad OTH AF: 0.00164

GnomAD2 exomes AF: 0.0000688 AC: 17 AN: 247162 AF XY: 0.0000746

Gnomad AFR exome AF: 0.000714

Gnomad AMR exome AF: 0.000146

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000556

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000282 AC: 41 AN: 1452348 Hom.: 1 Cov.: 83 AF XY: 0.0000263 AC XY: 19 AN XY: 722542

African (AFR) AF: 0.000512 AC: 17 AN: 33184

American (AMR) AF: 0.0000912 AC: 4 AN: 43868

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25854

East Asian (EAS) AF: 0.0000255 AC: 1 AN: 39180

South Asian (SAS) AF: 0.0000352 AC: 3 AN: 85346

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52278

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5734

European-Non Finnish (NFE) AF: 0.00000813 AC: 9 AN: 1107026

Other (OTH) AF: 0.000117 AC: 7 AN: 59878

GnomAD4 genome AF: 0.000211 AC: 28 AN: 132768 Hom.: 0 Cov.: 33 AF XY: 0.000278 AC XY: 18 AN XY: 64656

African (AFR) AF: 0.000580 AC: 20 AN: 34484

American (AMR) AF: 0.000295 AC: 4 AN: 13574

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3166

East Asian (EAS) AF: 0.00 AC: 0 AN: 4328

South Asian (SAS) AF: 0.00 AC: 0 AN: 4008

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8970

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 182

European-Non Finnish (NFE) AF: 0.0000163 AC: 1 AN: 61450

Other (OTH) AF: 0.00164 AC: 3 AN: 1826

Alfa AF: 0.000337 Hom.: 0

ExAC AF: 0.0000660 AC: 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	Benign	0.16
BayesDel_addAF	Benign	-0.67	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.95
DANN	Benign	0.27
DEOGEN2	Benign	0.00076	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.0039	N
LIST_S2	Benign	0.047	T
M_CAP	Benign	0.0010	T
MetaRNN	Benign	0.025	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.67	N
PhyloP100		-3.0
Sift4G	Benign	0.84	T
Polyphen		0.076	B
Vest4		0.027
MVP		0.11
MPC		0.066
ClinPred		0.0051	T
GERP RS		-1.8
Varity_R		0.015
gMVP		0.012
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: rs782512962; hg19: chr19-20807544; COSMIC: COSV74129035; COSMIC: COSV74129035;