19-36818959-C-T

Variant names:

• chr19-36818959-C-T
• NM_206894.4:c.1385G>A

Variant summary

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

The NM_206894.4(ZNF790):​c.1385G>A​(p.Gly462Asp) 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. 12/21 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: -0.805

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=0.14840552).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF790	NM_206894.4	c.1385G>A	p.Gly462Asp	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.1385G>A	p.Gly462Asp	missense_variant	Exon 5 of 5	2	NM_206894.4	ENSP00000349161.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 18, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1385G>A (p.G462D) 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 1385, causing the glycine (G) at amino acid position 462 to be replaced by an aspartic acid (D). 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	Pathogenic	0.59
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0042	T;T;T;T
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.65
FATHMM_MKL	Benign	0.0048	N
LIST_S2	Benign	0.65	.;T;.;.
M_CAP	Benign	0.0018	T
MetaRNN	Benign	0.15	T;T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.0	L;L;L;L
PrimateAI	Benign	0.32	T
PROVEAN	Uncertain	-2.4	N;.;.;.
REVEL	Benign	0.030
Sift	Benign	0.17	T;.;.;.
Sift4G	Benign	0.077	T;T;T;T
Polyphen		0.79	P;P;P;P
Vest4		0.16
MutPred		0.27		Gain of ubiquitination at K457 (P = 0.0497);Gain of ubiquitination at K457 (P = 0.0497);Gain of ubiquitination at K457 (P = 0.0497);Gain of ubiquitination at K457 (P = 0.0497);
MVP		0.47
MPC		0.29
ClinPred		0.49	T
GERP RS		2.1
Varity_R		0.073
gMVP		0.053

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-37309861;