X-153421347-G-C

Position:

• chrX-153421347-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001136273.2(ZFP92):​c.970G>C​(p.Glu324Gln) 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. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 26)
• Consequence: ZFP92 NM_001136273.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.50

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.098671645).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZFP92	NM_001136273.2	c.970G>C	p.Glu324Gln	missense_variant	6/6	ENST00000338647.7	NP_001129745.1
ZFP92	NM_001386944.1	c.970G>C	p.Glu324Gln	missense_variant	5/5		NP_001373873.1
ZFP92	NM_001386945.1	c.970G>C	p.Glu324Gln	missense_variant	7/7		NP_001373874.1
ZFP92	NM_001386943.1	c.844G>C	p.Glu282Gln	missense_variant	4/4		NP_001373872.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZFP92	ENST00000338647.7	c.970G>C	p.Glu324Gln	missense_variant	6/6	5	NM_001136273.2	ENSP00000462054.1

Frequencies

GnomAD3 genomes Cov.: 26

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 26

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 01, 2023

The c.970G>C (p.E324Q) alteration is located in exon 4 (coding exon 4) of the ZFP92 gene. This alteration results from a G to C substitution at nucleotide position 970, causing the glutamic acid (E) at amino acid position 324 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	0.31
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.93
CADD	Benign	14
DANN	Benign	0.68
DEOGEN2	Benign	0.029	T
FATHMM_MKL	Benign	0.012	N
LIST_S2	Benign	0.29	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.099	T
MutationAssessor	Benign	0.59	N
PrimateAI	Uncertain	0.60	T
Sift4G	Benign	0.19	T
Polyphen		0.033	B
Vest4		0.083
MVP		0.15
MPC		1.2
GERP RS		2.0
Varity_R		0.11
gMVP		0.46

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-152686805;