19-52510586-C-A

Variant names:

• chr19-52510586-C-A
• rs550019604
• NM_001099694.2:c.205C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001099694.2(ZNF578):​c.205C>A​(p.Arg69Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000072 in 1,387,996 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R69C) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: ZNF578 NM_001099694.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.03
• Publications: 0 publications found

Genes affected

ZNF578 (HGNC:26449): (zinc finger protein 578) 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 by RNA polymerase II. Predicted to be located in cytoplasm. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.037424147).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001099694.2. 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
	ZNF578	NM_001099694.2	MANE Select	c.205C>A	p.Arg69Ser	missense	Exon 6 of 6	NP_001093164.1	Q96N58
	ZNF578	NM_001366182.2		c.205C>A	p.Arg69Ser	missense	Exon 6 of 6	NP_001353111.1	Q96N58

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF578	ENST00000421239.7	TSL:2 MANE Select	c.205C>A	p.Arg69Ser	missense	Exon 6 of 6	ENSP00000459216.1	Q96N58
	ZNF578	ENST00000601120.1	TSL:5	c.205C>A	p.Arg69Ser	missense	Exon 4 of 4	ENSP00000470790.1	M0QZV4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.20e-7 AC: 1 AN: 1387996 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 684236

African (AFR) AF: 0.00 AC: 0 AN: 30746

American (AMR) AF: 0.00 AC: 0 AN: 31180

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21566

East Asian (EAS) AF: 0.00 AC: 0 AN: 39132

South Asian (SAS) AF: 0.00 AC: 0 AN: 73230

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50682

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5452

European-Non Finnish (NFE) AF: 9.27e-7 AC: 1 AN: 1078884

Other (OTH) AF: 0.00 AC: 0 AN: 57124

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	1.9
DANN	Benign	0.18
DEOGEN2	Benign	0.00095	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0042	N
LIST_S2	Benign	0.0068	T
M_CAP	Benign	0.00074	T
MetaRNN	Benign	0.037	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-1.1	N
PhyloP100		-1.0
Sift4G	Benign	0.75	T
Vest4		0.058
MVP		0.030
MPC		0.030
ClinPred		0.14	T
GERP RS		-1.2
Varity_R		0.075
gMVP		0.028
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs550019604; hg19: chr19-53013839;