chr19-36819004-C-T

Variant names:

• chr19-36819004-C-T
• rs761740560
• NM_206894.4:c.1340G>A

Variant summary

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

The NM_206894.4(ZNF790):​c.1340G>A​(p.Arg447Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000506 in 1,461,574 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000051 (0 hom.)
• Consequence: ZNF790 NM_206894.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0520
• 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: 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=0.052538425).

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.1340G>A	p.Arg447Lys	missense	Exon 5 of 5	NP_996777.2	Q6PG37
	ZNF790	NM_001242800.2		c.1340G>A	p.Arg447Lys	missense	Exon 5 of 5	NP_001229729.1	Q6PG37
	ZNF790	NM_001242801.2		c.1340G>A	p.Arg447Lys	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.1340G>A	p.Arg447Lys	missense	Exon 5 of 5	ENSP00000349161.3	Q6PG37
	ZNF790	ENST00000613249.4	TSL:4	c.1340G>A	p.Arg447Lys	missense	Exon 5 of 5	ENSP00000480764.1	Q6PG37
	ZNF790	ENST00000614179.4	TSL:3	c.1340G>A	p.Arg447Lys	missense	Exon 5 of 5	ENSP00000480834.1	Q6PG37

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000199 AC: 5 AN: 251166 AF XY: 0.0000147

Gnomad AFR exome AF: 0.0000616

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: 0.0000352

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000506 AC: 74 AN: 1461574 Hom.: 0 Cov.: 32 AF XY: 0.0000578 AC XY: 42 AN XY: 727094

African (AFR) AF: 0.0000598 AC: 2 AN: 33472

American (AMR) AF: 0.00 AC: 0 AN: 44674

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26114

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86218

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53380

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000630 AC: 70 AN: 1111872

Other (OTH) AF: 0.0000331 AC: 2 AN: 60382

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000565 Hom.: 0

Bravo AF: 0.00000378

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ExAC AF: 0.00000824 AC: 1

EpiCase AF: 0.000109

EpiControl AF: 0.0000593

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	0.074
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	6.5
DANN	Benign	0.97
DEOGEN2	Benign	0.0013	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.00071	N
LIST_S2	Benign	0.27	T
M_CAP	Benign	0.00091	T
MetaRNN	Benign	0.053	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-0.28	N
PhyloP100		0.052
PrimateAI	Benign	0.28	T
PROVEAN	Benign	0.84	N
REVEL	Benign	0.069
Sift	Uncertain	0.017	D
Sift4G	Benign	0.076	T
Polyphen		0.0	B
Vest4		0.081
MutPred		0.41		Gain of methylation at R447 (P = 0.0093)
MVP		0.30
MPC		0.052
ClinPred		0.069	T
GERP RS		-0.33
Varity_R		0.053
gMVP		0.040
Mutation Taster		=96/4	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: rs761740560; hg19: chr19-37309906;