NM_206894.4:c.1603G>A

Variant names:

• chr19-36818741-C-T
• rs199662090
• NM_206894.4:c.1603G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_206894.4(ZNF790):​c.1603G>A​(p.Val535Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000115 in 1,612,322 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000098 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00012 (0 hom.)
• Consequence: ZNF790 NM_206894.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -5.62
• Publications: 3 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.01178965).

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.1603G>A	p.Val535Ile	missense	Exon 5 of 5	NP_996777.2	Q6PG37
	ZNF790	NM_001242800.2		c.1603G>A	p.Val535Ile	missense	Exon 5 of 5	NP_001229729.1	Q6PG37
	ZNF790	NM_001242801.2		c.1603G>A	p.Val535Ile	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.1603G>A	p.Val535Ile	missense	Exon 5 of 5	ENSP00000349161.3	Q6PG37
	ZNF790	ENST00000613249.4	TSL:4	c.1603G>A	p.Val535Ile	missense	Exon 5 of 5	ENSP00000480764.1	Q6PG37
	ZNF790	ENST00000614179.4	TSL:3	c.1603G>A	p.Val535Ile	missense	Exon 5 of 5	ENSP00000480834.1	Q6PG37

Frequencies

GnomAD3 genomes AF: 0.0000986 AC: 15 AN: 152170 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000771

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000128 AC: 32 AN: 249050 AF XY: 0.000126

Gnomad AFR exome AF: 0.0000618

Gnomad AMR exome AF: 0.0000885

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000982

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000886

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000117 AC: 171 AN: 1460034 Hom.: 0 Cov.: 31 AF XY: 0.000116 AC XY: 84 AN XY: 726436

African (AFR) AF: 0.0000300 AC: 1 AN: 33286

American (AMR) AF: 0.0000679 AC: 3 AN: 44210

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25974

East Asian (EAS) AF: 0.00144 AC: 57 AN: 39684

South Asian (SAS) AF: 0.00 AC: 0 AN: 86102

European-Finnish (FIN) AF: 0.0000188 AC: 1 AN: 53332

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.0000900 AC: 100 AN: 1111402

Other (OTH) AF: 0.000149 AC: 9 AN: 60286

GnomAD4 genome AF: 0.0000985 AC: 15 AN: 152288 Hom.: 0 Cov.: 32 AF XY: 0.0000940 AC XY: 7 AN XY: 74466

African (AFR) AF: 0.0000963 AC: 4 AN: 41558

American (AMR) AF: 0.00 AC: 0 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000772 AC: 4 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.0000657 Hom.: 0

Bravo AF: 0.0000982

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.000140 AC: 17

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.000178

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	0.069
BayesDel_addAF	Benign	-0.69	T
BayesDel_noAF	Benign	-0.82
CADD	Benign	10
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0012	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.019	N
LIST_S2	Benign	0.049	T
M_CAP	Benign	0.00079	T
MetaRNN	Benign	0.012	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.80	N
PhyloP100		-5.6
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.79	N
REVEL	Benign	0.016
Sift	Benign	0.083	T
Sift4G	Uncertain	0.014	D
Polyphen		0.0050	B
Vest4		0.038
MVP		0.17
MPC		0.043
ClinPred		0.023	T
GERP RS		-1.6
Varity_R		0.030
gMVP		0.012
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

Other links and lift over

dbSNP: rs199662090; hg19: chr19-37309643; COSMIC: COSV63213001; COSMIC: COSV63213001;