chr19-34958260-C-T

Variant names:

• chr19-34958260-C-T
• rs145626872
• NM_175872.5:c.1595G>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.1595G>A​(p.Arg532Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000793 in 1,613,328 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. R532W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00037 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000049 (0 hom.)
• Consequence: ZNF792 NM_175872.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.141
• 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.020822853).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF792	NM_175872.5	c.1595G>A	p.Arg532Gln	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.1595G>A	p.Arg532Gln	missense_variant	Exon 4 of 4	2	NM_175872.5	ENSP00000385099.1
ZNF792	ENST00000605484.1	c.1394G>A	p.Arg465Gln	missense_variant	Exon 2 of 2	1		ENSP00000474130.1

Frequencies

GnomAD3 genomes AF: 0.000369 AC: 56 AN: 151670 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00116

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000656

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000209

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000884

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000127 AC: 32 AN: 251262 AF XY: 0.000147

Gnomad AFR exome AF: 0.00123

Gnomad AMR exome AF: 0.0000579

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000880

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000493 AC: 72 AN: 1461538 Hom.: 0 Cov.: 34 AF XY: 0.0000564 AC XY: 41 AN XY: 727028

African (AFR) AF: 0.000926 AC: 31 AN: 33470

American (AMR) AF: 0.0000895 AC: 4 AN: 44682

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39670

South Asian (SAS) AF: 0.000232 AC: 20 AN: 86192

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53412

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000117 AC: 13 AN: 1111842

Other (OTH) AF: 0.0000331 AC: 2 AN: 60372

GnomAD4 genome AF: 0.000369 AC: 56 AN: 151790 Hom.: 0 Cov.: 32 AF XY: 0.000350 AC XY: 26 AN XY: 74214

African (AFR) AF: 0.00116 AC: 48 AN: 41372

American (AMR) AF: 0.0000655 AC: 1 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5134

South Asian (SAS) AF: 0.000209 AC: 1 AN: 4776

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 288

European-Non Finnish (NFE) AF: 0.0000884 AC: 6 AN: 67862

Other (OTH) AF: 0.00 AC: 0 AN: 2102

Alfa AF: 0.000197 Hom.: 0

Bravo AF: 0.000348

ESP6500AA AF: 0.000908 AC: 4

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.000157 AC: 19

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 30, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1595G>A (p.R532Q) 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 1595, causing the arginine (R) at amino acid position 532 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	Pathogenic	0.74
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	22
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.10	T;T
Eigen	Benign	-0.080
Eigen_PC	Benign	-0.32
FATHMM_MKL	Benign	0.0013	N
LIST_S2	Benign	0.43	T;T
M_CAP	Benign	0.034	D
MetaRNN	Benign	0.021	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.2	M;.
PhyloP100		-0.14
PrimateAI	Uncertain	0.59	T
PROVEAN	Uncertain	-2.9	D;.
REVEL	Benign	0.095
Sift	Uncertain	0.0040	D;.
Sift4G	Uncertain	0.011	D;D
Polyphen		1.0	D;.
Vest4		0.084
MVP		0.31
MPC		0.66
ClinPred		0.11	T
GERP RS		1.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.19
gMVP		0.11
Mutation Taster		=99/1	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: rs145626872; hg19: chr19-35449164; COSMIC: COSV101289703;