19-36818821-C-G

Variant names:

• chr19-36818821-C-G
• rs769270489
• NM_206894.4:c.1523G>C

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_206894.4(ZNF790):​c.1523G>C​(p.Cys508Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,396 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. C508Y) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ZNF790 NM_206894.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.70
• Publications: 0 publications found

Genes affected

ZNF790 (HGNC:33114): (zinc finger protein 790) 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 active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF790-AS1 (HGNC:27617): (ZNF790 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.819

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_206894.4. 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
	ZNF790	NM_206894.4	MANE Select	c.1523G>C	p.Cys508Ser	missense	Exon 5 of 5	NP_996777.2	Q6PG37
	ZNF790	NM_001242800.2		c.1523G>C	p.Cys508Ser	missense	Exon 5 of 5	NP_001229729.1	Q6PG37
	ZNF790	NM_001242801.2		c.1523G>C	p.Cys508Ser	missense	Exon 5 of 5	NP_001229730.1	Q6PG37

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF790	ENST00000356725.9	TSL:2 MANE Select	c.1523G>C	p.Cys508Ser	missense	Exon 5 of 5	ENSP00000349161.3	Q6PG37
	ZNF790	ENST00000613249.4	TSL:4	c.1523G>C	p.Cys508Ser	missense	Exon 5 of 5	ENSP00000480764.1	Q6PG37
	ZNF790	ENST00000614179.4	TSL:3	c.1523G>C	p.Cys508Ser	missense	Exon 5 of 5	ENSP00000480834.1	Q6PG37

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460396 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 726460

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33374

American (AMR) AF: 0.00 AC: 0 AN: 44432

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26038

East Asian (EAS) AF: 0.00 AC: 0 AN: 39676

South Asian (SAS) AF: 0.00 AC: 0 AN: 86134

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53316

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5752

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111354

Other (OTH) AF: 0.00 AC: 0 AN: 60320

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.87
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.35	T
Eigen	Uncertain	0.64
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.46	T
M_CAP	Benign	0.012	T
MetaRNN	Pathogenic	0.82	D
MetaSVM	Pathogenic	0.87	D
MutationAssessor	Pathogenic	3.0	M
PhyloP100		1.7
PrimateAI	Uncertain	0.62	T
PROVEAN	Pathogenic	-9.0	D
REVEL	Uncertain	0.56
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.55
MutPred		0.74		Gain of disorder (P = 0.0324)
MVP		0.88
MPC		0.36
ClinPred		1.0	D
GERP RS		3.0
Varity_R		0.88
gMVP		0.24
Mutation Taster		=92/8	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: rs769270489; hg19: chr19-37309723;