X-153421078-G-A

Variant names:

• chrX-153421078-G-A
• rs868992296
• NM_001136273.2:c.701G>A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001136273.2(ZFP92):​c.701G>A​(p.Arg234Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000373 in 1,071,922 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 26)
  • Exomes 𝑓: 0.0000037 (0 hom. 2 hem.)
• Consequence: ZFP92 NM_001136273.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0850

Genes affected

ZFP92 (HGNC:12865): (ZFP92 zinc finger protein) 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]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.07747963).
• BS2: High Hemizygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZFP92	NM_001136273.2	c.701G>A	p.Arg234Gln	missense_variant	Exon 6 of 6	ENST00000338647.7	NP_001129745.1
ZFP92	NM_001386944.1	c.701G>A	p.Arg234Gln	missense_variant	Exon 5 of 5		NP_001373873.1
ZFP92	NM_001386945.1	c.701G>A	p.Arg234Gln	missense_variant	Exon 7 of 7		NP_001373874.1
ZFP92	NM_001386943.1	c.575G>A	p.Arg192Gln	missense_variant	Exon 4 of 4		NP_001373872.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZFP92	ENST00000338647.7	c.701G>A	p.Arg234Gln	missense_variant	Exon 6 of 6	5	NM_001136273.2	ENSP00000462054.1

Frequencies

GnomAD3 genomes Cov.: 26

GnomAD4 exome AF: 0.00000373 AC: 4 AN: 1071922 Hom.: 0 Cov.: 31 AF XY: 0.00000576 AC XY: 2 AN XY: 347364

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000482

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 26

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 08, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.701G>A (p.R234Q) alteration is located in exon 4 (coding exon 4) of the ZFP92 gene. This alteration results from a G to A substitution at nucleotide position 701, causing the arginine (R) at amino acid position 234 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	Uncertain	0.54
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.93
CADD	Benign	13
DANN	Benign	0.92
DEOGEN2	Benign	0.038	T
FATHMM_MKL	Benign	0.033	N
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.077	T
MutationAssessor	Uncertain	2.2	M
PrimateAI	Uncertain	0.52	T
Sift4G	Uncertain	0.0030	D
Polyphen		0.88	P
Vest4		0.090
MVP		0.20
MPC		1.2
GERP RS		-0.79
Varity_R		0.049
gMVP		0.23

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

LitVar

Other links and lift over

dbSNP: rs868992296; hg19: chrX-152686536;