X-153421620-C-T

Position:

• chrX-153421620-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001136273.2(ZFP92):​c.1243C>T​(p.Arg415Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000687 in 873,625 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 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: 26)
  • Exomes 𝑓: 0.0000069 (0 hom. 3 hem.)
• Consequence: ZFP92 NM_001136273.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -3.06

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 Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.046554446).
• BS2: High Hemizygotes in GnomAdExome4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZFP92	NM_001136273.2	c.1243C>T	p.Arg415Cys	missense_variant	6/6	ENST00000338647.7	NP_001129745.1
ZFP92	NM_001386944.1	c.1243C>T	p.Arg415Cys	missense_variant	5/5		NP_001373873.1
ZFP92	NM_001386945.1	c.1243C>T	p.Arg415Cys	missense_variant	7/7		NP_001373874.1
ZFP92	NM_001386943.1	c.1117C>T	p.Arg373Cys	missense_variant	4/4		NP_001373872.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZFP92	ENST00000338647.7	c.1243C>T	p.Arg415Cys	missense_variant	6/6	5	NM_001136273.2	ENSP00000462054	P1

Frequencies

GnomAD3 genomes Cov.: 26

GnomAD4 exome AF: 0.00000687 AC: 6 AN: 873625 Hom.: 0 Cov.: 30 AF XY: 0.0000111 AC XY: 3 AN XY: 270229

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: 0.00000545

Gnomad4 OTH exome AF: 0.0000564

GnomAD4 genome Cov.: 26

Bravo AF: 0.00000378

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

Oct 13, 2023

The c.1243C>T (p.R415C) alteration is located in exon 4 (coding exon 4) of the ZFP92 gene. This alteration results from a C to T substitution at nucleotide position 1243, causing the arginine (R) at amino acid position 415 to be replaced by a cysteine (C). 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	0.22
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-1.1
CADD	Benign	8.1
DANN	Benign	0.86
DEOGEN2	Benign	0.0080	T
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.60	T
M_CAP	Benign	0.078	D
MetaRNN	Benign	0.047	T
MutationAssessor	Benign	0.0	N
MutationTaster	Benign	1.0	N
PrimateAI	Uncertain	0.53	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.0010	B
Vest4		0.068
MVP		0.068
MPC		1.3
GERP RS		-4.8
Varity_R		0.082
gMVP		0.27

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: rs1321141593; hg19: chrX-152687078;