chr19-34958136-T-G

Variant names:

• chr19-34958136-T-G
• NM_175872.5:c.1719A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_175872.5(ZNF792):​c.1719A>C​(p.Gln573His) 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. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF792 NM_175872.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.582
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07249498).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF792	NM_175872.5	c.1719A>C	p.Gln573His	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.1719A>C	p.Gln573His	missense_variant	Exon 4 of 4	2	NM_175872.5	ENSP00000385099.1
ZNF792	ENST00000605484.1	c.1518A>C	p.Gln506His	missense_variant	Exon 2 of 2	1		ENSP00000474130.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 20, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1719A>C (p.Q573H) alteration is located in exon 4 (coding exon 4) of the ZNF792 gene. This alteration results from a A to C substitution at nucleotide position 1719, causing the glutamine (Q) at amino acid position 573 to be replaced by a histidine (H). 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	0.82
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	16
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0061	T;T
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.84
FATHMM_MKL	Benign	0.00044	N
LIST_S2	Benign	0.33	T;T
M_CAP	Benign	0.0029	T
MetaRNN	Benign	0.072	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.22	N;.
PhyloP100		-0.58
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-0.73	N;.
REVEL	Benign	0.078
Sift	Benign	0.50	T;.
Sift4G	Benign	0.31	T;T
Polyphen		0.96	D;.
Vest4		0.21
MutPred		0.44		Loss of MoRF binding (P = 0.1054);.;
MVP		0.17
MPC		0.15
ClinPred		0.14	T
GERP RS		-1.1
Varity_R		0.025
gMVP		0.23
Mutation Taster		=97/3	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

hg19: chr19-35449040;