X-153418348-G-C

Position:

• chrX-153418348-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.26G>C​(p.Arg9Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000285 in 1,054,042 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. 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: 23)
  • Exomes 𝑓: 0.0000028 (0 hom. 1 hem.)
• Consequence: ZFP92 NM_001136273.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.92

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=0.17524686).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZFP92	NM_001136273.2	c.26G>C	p.Arg9Thr	missense_variant	3/6	ENST00000338647.7	NP_001129745.1
ZFP92	NM_001386944.1	c.26G>C	p.Arg9Thr	missense_variant	2/5		NP_001373873.1
ZFP92	NM_001386945.1	c.26G>C	p.Arg9Thr	missense_variant	4/7		NP_001373874.1
ZFP92	NM_001386943.1	c.-93-325G>C		intron_variant			NP_001373872.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZFP92	ENST00000338647.7	c.26G>C	p.Arg9Thr	missense_variant	3/6	5	NM_001136273.2	ENSP00000462054.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 0.00000285 AC: 3 AN: 1054042 Hom.: 0 Cov.: 31 AF XY: 0.00000290 AC XY: 1 AN XY: 344850

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: 0.0000201

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000451

GnomAD4 genome Cov.: 23

Bravo AF: 0.0000113

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

Dec 28, 2022

The c.26G>C (p.R9T) alteration is located in exon 1 (coding exon 1) of the ZFP92 gene. This alteration results from a G to C substitution at nucleotide position 26, causing the arginine (R) at amino acid position 9 to be replaced by a threonine (T). 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	0.15
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	18
DANN	Benign	0.57
DEOGEN2	Benign	0.027	T
FATHMM_MKL	Benign	0.083	N
LIST_S2	Benign	0.10	T
M_CAP	Uncertain	0.16	D
MetaRNN	Benign	0.18	T
MutationAssessor	Benign	0.28	N
PrimateAI	Benign	0.46	T
Sift4G	Benign	0.52	T
Polyphen		0.90	P
Vest4		0.33
MVP		0.23
MPC		2.3
GERP RS		3.0
Varity_R		0.12
gMVP		0.14

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: rs2088971371; hg19: chrX-152683806;