19-34958281-C-T

Variant names:

• chr19-34958281-C-T
• rs200516958
• NM_175872.5:c.1574G>A

Variant summary

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

The NM_175872.5(ZNF792):​c.1574G>A​(p.Arg525Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000272 in 1,604,408 control chromosomes in the GnomAD database, including 1 homozygotes. 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 0.00020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00028 (1 hom.)
• Consequence: ZNF792 NM_175872.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.26
• Publications: 2 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.018270135).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF792	NM_175872.5	c.1574G>A	p.Arg525Gln	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.1574G>A	p.Arg525Gln	missense_variant	Exon 4 of 4	2	NM_175872.5	ENSP00000385099.1
ZNF792	ENST00000605484.1	c.1373G>A	p.Arg458Gln	missense_variant	Exon 2 of 2	1		ENSP00000474130.1

Frequencies

GnomAD3 genomes AF: 0.000200 AC: 29 AN: 144860 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000154

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000206

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000335

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000159 AC: 40 AN: 250898 AF XY: 0.000192

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.000116

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000300

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000280 AC: 408 AN: 1459422 Hom.: 1 Cov.: 36 AF XY: 0.000288 AC XY: 209 AN XY: 725996

African (AFR) AF: 0.0000299 AC: 1 AN: 33396

American (AMR) AF: 0.000181 AC: 8 AN: 44142

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26064

East Asian (EAS) AF: 0.00 AC: 0 AN: 39420

South Asian (SAS) AF: 0.0000233 AC: 2 AN: 85826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53400

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5762

European-Non Finnish (NFE) AF: 0.000348 AC: 387 AN: 1111128

Other (OTH) AF: 0.000149 AC: 9 AN: 60284

GnomAD4 genome AF: 0.000200 AC: 29 AN: 144986 Hom.: 0 Cov.: 32 AF XY: 0.000141 AC XY: 10 AN XY: 70924

African (AFR) AF: 0.000154 AC: 6 AN: 39050

American (AMR) AF: 0.00 AC: 0 AN: 14706

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3346

East Asian (EAS) AF: 0.000207 AC: 1 AN: 4834

South Asian (SAS) AF: 0.00 AC: 0 AN: 4472

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9896

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 240

European-Non Finnish (NFE) AF: 0.000335 AC: 22 AN: 65580

Other (OTH) AF: 0.00 AC: 0 AN: 2002

Alfa AF: 0.000251 Hom.: 0

Bravo AF: 0.000185

TwinsUK AF: 0.00108 AC: 4

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.000681 AC: 3

ESP6500EA AF: 0.000465 AC: 4

ExAC AF: 0.000181 AC: 22

EpiCase AF: 0.000436

EpiControl AF: 0.000534

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 16, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1574G>A (p.R525Q) alteration is located in exon 4 (coding exon 4) of the ZNF792 gene. This alteration results from a G to A substitution at nucleotide position 1574, causing the arginine (R) at amino acid position 525 to be replaced by a glutamine (Q). 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	0.12
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.00077	T;T
Eigen	Benign	-0.84
Eigen_PC	Benign	-0.83
FATHMM_MKL	Benign	0.00047	N
LIST_S2	Benign	0.52	T;T
M_CAP	Benign	0.0060	T
MetaRNN	Benign	0.018	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.10	N;.
PhyloP100		-1.3
PrimateAI	Benign	0.43	T
PROVEAN	Benign	0.55	N;.
REVEL	Benign	0.071
Sift	Benign	0.79	T;.
Sift4G	Benign	0.91	T;T
Polyphen		0.67	P;.
Vest4		0.047
MVP		0.14
MPC		0.20
ClinPred		0.028	T
GERP RS		1.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.070
gMVP		0.11
Mutation Taster		=93/7	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: rs200516958; hg19: chr19-35449185;