19-36818815-T-C

Variant names:

• chr19-36818815-T-C
• rs775961438
• NM_206894.4:c.1529A>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_206894.4(ZNF790):​c.1529A>G​(p.Glu510Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,460,052 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E510Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: ZNF790 NM_206894.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.852

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20539051).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF790	NM_206894.4	c.1529A>G	p.Glu510Gly	missense_variant	Exon 5 of 5	ENST00000356725.9	NP_996777.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF790	ENST00000356725.9	c.1529A>G	p.Glu510Gly	missense_variant	Exon 5 of 5	2	NM_206894.4	ENSP00000349161.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.0000320 AC: 8 AN: 249864 Hom.: 0 AF XY: 0.0000296 AC XY: 4 AN XY: 135134

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000436

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000411 AC: 6 AN: 1460052 Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3 AN XY: 726292

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000126

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000756

ExAC AF: 0.00000824 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 18, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1529A>G (p.E510G) alteration is located in exon 5 (coding exon 4) of the ZNF790 gene. This alteration results from a A to G substitution at nucleotide position 1529, causing the glutamic acid (E) at amino acid position 510 to be replaced by a glycine (G). 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	0.23
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.45
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.048	T;T;T;T
Eigen	Benign	0.10
Eigen_PC	Benign	-0.022
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.092	.;T;.;.
M_CAP	Benign	0.0023	T
MetaRNN	Benign	0.21	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L;L;L;L
PrimateAI	Benign	0.33	T
PROVEAN	Pathogenic	-5.0	D;.;.;.
REVEL	Benign	0.064
Sift	Uncertain	0.0010	D;.;.;.
Sift4G	Uncertain	0.0070	D;D;D;D
Polyphen		0.99	D;D;D;D
Vest4		0.18
MutPred		0.50		Loss of stability (P = 0.0548);Loss of stability (P = 0.0548);Loss of stability (P = 0.0548);Loss of stability (P = 0.0548);
MVP		0.63
MPC		0.34
ClinPred		0.59	D
GERP RS		3.0
Varity_R		0.36
gMVP		0.043

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: rs775961438; hg19: chr19-37309717;