X-153421267-G-A

Variant names:

• chrX-153421267-G-A
• NM_001136273.2:c.890G>A

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001136273.2(ZFP92):​c.890G>A​(p.Cys297Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000944 in 1,059,718 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 27)
  • Exomes 𝑓: 9.4e-7 (0 hom. 0 hem.)
• Consequence: ZFP92 NM_001136273.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.19
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.916

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001136273.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZFP92	NM_001136273.2	MANE Select	c.890G>A	p.Cys297Tyr	missense	Exon 6 of 6	NP_001129745.1	A6NM28
	ZFP92	NM_001386944.1		c.890G>A	p.Cys297Tyr	missense	Exon 5 of 5	NP_001373873.1	A6NM28
	ZFP92	NM_001386945.1		c.890G>A	p.Cys297Tyr	missense	Exon 7 of 7	NP_001373874.1	A6NM28

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZFP92	ENST00000338647.7	TSL:5 MANE Select	c.890G>A	p.Cys297Tyr	missense	Exon 6 of 6	ENSP00000462054.1	A6NM28
	ZFP92	ENST00000881745.1		c.890G>A	p.Cys297Tyr	missense	Exon 5 of 5	ENSP00000551804.1

Frequencies

GnomAD3 genomes Cov.: 27

GnomAD4 exome AF: 9.44e-7 AC: 1 AN: 1059718 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 344404

African (AFR) AF: 0.00 AC: 0 AN: 25193

American (AMR) AF: 0.00 AC: 0 AN: 29080

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18702

East Asian (EAS) AF: 0.00 AC: 0 AN: 27748

South Asian (SAS) AF: 0.00 AC: 0 AN: 50507

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35826

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4084

European-Non Finnish (NFE) AF: 0.00000121 AC: 1 AN: 823899

Other (OTH) AF: 0.00 AC: 0 AN: 44679

GnomAD4 genome Cov.: 27

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.52	D
BayesDel_noAF	Pathogenic	0.51
CADD	Uncertain	25
DANN	Benign	0.95
DEOGEN2	Uncertain	0.47	T
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.80	T
M_CAP	Pathogenic	0.62	D
MetaRNN	Pathogenic	0.92	D
MutationAssessor	Pathogenic	3.6	H
PhyloP100		9.2
PrimateAI	Pathogenic	0.92	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.70
MVP		0.98
MPC		2.7
GERP RS		3.0
Varity_R		0.39
gMVP		0.99
Mutation Taster		=91/9	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

hg19: chrX-152686725;