chr19-36818821-C-T

Variant names:

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

Variant summary

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

The NM_206894.4(ZNF790):​c.1523G>A​(p.Cys508Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000403 in 1,612,552 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000044 (0 hom.)
• Consequence: ZNF790 NM_206894.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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 0 ACMG points.

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>A	p.Cys508Tyr	missense	Exon 5 of 5	NP_996777.2	Q6PG37
	ZNF790	NM_001242800.2		c.1523G>A	p.Cys508Tyr	missense	Exon 5 of 5	NP_001229729.1	Q6PG37
	ZNF790	NM_001242801.2		c.1523G>A	p.Cys508Tyr	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>A	p.Cys508Tyr	missense	Exon 5 of 5	ENSP00000349161.3	Q6PG37
	ZNF790	ENST00000613249.4	TSL:4	c.1523G>A	p.Cys508Tyr	missense	Exon 5 of 5	ENSP00000480764.1	Q6PG37
	ZNF790	ENST00000614179.4	TSL:3	c.1523G>A	p.Cys508Tyr	missense	Exon 5 of 5	ENSP00000480834.1	Q6PG37

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152156 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000999 AC: 25 AN: 250184 AF XY: 0.000103

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000165

GnomAD4 exome AF: 0.0000438 AC: 64 AN: 1460396 Hom.: 0 Cov.: 32 AF XY: 0.0000592 AC XY: 43 AN XY: 726460

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: 0.000708 AC: 61 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: 0.00 AC: 0 AN: 1111354

Other (OTH) AF: 0.0000497 AC: 3 AN: 60320

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152156 Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1 AN XY: 74326

African (AFR) AF: 0.00 AC: 0 AN: 41436

American (AMR) AF: 0.00 AC: 0 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000341 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.000107 AC: 13

Asia WGS AF: 0.000866 AC: 3 AN: 3478

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	Pathogenic	0.76
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Uncertain	-0.050
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.39	T
Eigen	Uncertain	0.65
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.64	T
M_CAP	Benign	0.016	T
MetaRNN	Uncertain	0.53	D
MetaSVM	Pathogenic	0.85	D
MutationAssessor	Pathogenic	3.4	M
PhyloP100		1.7
PrimateAI	Uncertain	0.69	T
PROVEAN	Pathogenic	-9.8	D
REVEL	Uncertain	0.51
Sift	Uncertain	0.0040	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.49
MutPred		0.74		Gain of phosphorylation at C508 (P = 0.0699)
MVP		0.90
MPC		0.41
ClinPred		0.99	D
GERP RS		3.0
Varity_R		0.84
gMVP		0.32
Mutation Taster		=93/7	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; COSMIC: COSV105912661; COSMIC: COSV105912661;