19-20624884-A-C

Variant names:

• chr19-20624884-A-C
• NM_001076675.3:c.993T>G
• ZNF626 p.His331Gln

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001076675.3(ZNF626):​c.993T>G​(p.His331Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 11/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF626 NM_001076675.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.470
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.993T>G	p.His331Gln	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.993T>G	p.His331Gln	missense	Exon 4 of 4	ENSP00000469958.1	Q68DY1-1
	ENSG00000269110	ENST00000595094.1	TSL:5	n.363+20800T>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 83

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.91
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	18
DANN	Benign	0.92
DEOGEN2	Benign	0.15	T
Eigen	Benign	-0.17
Eigen_PC	Benign	-0.56
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.38	T
M_CAP	Benign	0.0018	T
MetaRNN	Uncertain	0.60	D
MetaSVM	Uncertain	-0.15	T
MutationAssessor	Pathogenic	3.7	H
PhyloP100		-0.47
Sift4G	Uncertain	0.0050	D
Varity_R		0.31
gMVP		0.045
Mutation Taster		=99/1	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr19-20807690;