chr19-36818909-C-T

Position:

• chr19-36818909-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_206894.4(ZNF790):​c.1435G>A​(p.Glu479Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 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)
• Consequence: ZNF790 NM_206894.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.11

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.033709794).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF790	NM_206894.4	c.1435G>A	p.Glu479Lys	missense_variant	5/5	ENST00000356725.9	NP_996777.2
ZNF790-AS1	NR_040027.1	n.359-4822C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF790	ENST00000356725.9	c.1435G>A	p.Glu479Lys	missense_variant	5/5	2	NM_206894.4	ENSP00000349161	P1
ZNF790-AS1	ENST00000650959.1	n.477+5877C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

Bravo AF: 0.0000151

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 02, 2023

The c.1435G>A (p.E479K) alteration is located in exon 5 (coding exon 4) of the ZNF790 gene. This alteration results from a G to A substitution at nucleotide position 1435, causing the glutamic acid (E) at amino acid position 479 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0035	T;T;T;T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0074	N
LIST_S2	Benign	0.18	.;T;.;.
M_CAP	Benign	0.00068	T
MetaRNN	Benign	0.034	T;T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	-0.72	N;N;N;N
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-2.1	N;.;.;.
REVEL	Benign	0.024
Sift	Benign	0.22	T;.;.;.
Sift4G	Benign	0.30	T;T;T;T
Polyphen		0.0040	B;B;B;B
Vest4		0.14
MutPred		0.44		Gain of methylation at E479 (P = 2e-04);Gain of methylation at E479 (P = 2e-04);Gain of methylation at E479 (P = 2e-04);Gain of methylation at E479 (P = 2e-04);
MVP		0.18
MPC		0.070
ClinPred		0.088	T
GERP RS		-3.6
Varity_R		0.044
gMVP		0.032

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

Publications

LitVar

Other links and lift over

dbSNP: rs1380719004; hg19: chr19-37309811;