19-34958261-G-A

Variant names:

• chr19-34958261-G-A
• rs768051045
• NM_175872.5:c.1594C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_175872.5(ZNF792):​c.1594C>T​(p.Arg532Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000713 in 1,612,448 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. R532Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000074 (0 hom.)
• Consequence: ZNF792 NM_175872.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.12
• Publications: 0 publications found

Genes affected

ZNF792 (HGNC:24751): (zinc finger protein 792) Enables identical protein 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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.123711914).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF792	NM_175872.5	c.1594C>T	p.Arg532Trp	missense_variant	Exon 4 of 4	ENST00000404801.2	NP_787068.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF792	ENST00000404801.2	c.1594C>T	p.Arg532Trp	missense_variant	Exon 4 of 4	2	NM_175872.5	ENSP00000385099.1
ZNF792	ENST00000605484.1	c.1393C>T	p.Arg465Trp	missense_variant	Exon 2 of 2	1		ENSP00000474130.1

Frequencies

GnomAD3 genomes AF: 0.0000462 AC: 7 AN: 151402 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000486

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000391

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000442

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000557 AC: 14 AN: 251160 AF XY: 0.0000589

Gnomad AFR exome AF: 0.0000616

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000880

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000739 AC: 108 AN: 1461046 Hom.: 0 Cov.: 35 AF XY: 0.0000771 AC XY: 56 AN XY: 726780

African (AFR) AF: 0.0000299 AC: 1 AN: 33456

American (AMR) AF: 0.0000224 AC: 1 AN: 44562

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26122

East Asian (EAS) AF: 0.000202 AC: 8 AN: 39646

South Asian (SAS) AF: 0.0000581 AC: 5 AN: 86026

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.0000774 AC: 86 AN: 1111696

Other (OTH) AF: 0.0000994 AC: 6 AN: 60364

GnomAD4 genome AF: 0.0000462 AC: 7 AN: 151402 Hom.: 0 Cov.: 32 AF XY: 0.0000676 AC XY: 5 AN XY: 73932

African (AFR) AF: 0.0000486 AC: 2 AN: 41186

American (AMR) AF: 0.00 AC: 0 AN: 15216

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3462

East Asian (EAS) AF: 0.000391 AC: 2 AN: 5114

South Asian (SAS) AF: 0.00 AC: 0 AN: 4756

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10574

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 310

European-Non Finnish (NFE) AF: 0.0000442 AC: 3 AN: 67798

Other (OTH) AF: 0.00 AC: 0 AN: 2078

Alfa AF: 0.0000745 Hom.: 0

Bravo AF: 0.0000567

ExAC AF: 0.0000576 AC: 7

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000327

EpiControl AF: 0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 23, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1594C>T (p.R532W) alteration is located in exon 4 (coding exon 4) of the ZNF792 gene. This alteration results from a C to T substitution at nucleotide position 1594, causing the arginine (R) at amino acid position 532 to be replaced by a tryptophan (W). 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	0.85
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.22
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.28	T;T
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.48
FATHMM_MKL	Benign	0.0043	N
LIST_S2	Benign	0.45	T;T
M_CAP	Benign	0.0090	T
MetaRNN	Benign	0.12	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Pathogenic	3.0	M;.
PhyloP100		1.1
PrimateAI	Uncertain	0.69	T
PROVEAN	Pathogenic	-6.2	D;.
REVEL	Benign	0.12
Sift	Pathogenic	0.0	D;.
Sift4G	Pathogenic	0.0010	D;D
Polyphen		0.78	P;.
Vest4		0.26
MVP		0.40
MPC		0.67
ClinPred		0.61	D
GERP RS		0.34
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.42
gMVP		0.22
Mutation Taster		=95/5	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: rs768051045; hg19: chr19-35449165; COSMIC: COSV101289704;