X-153421308-C-T

Variant names:

• chrX-153421308-C-T
• rs2089000466
• NM_001136273.2:c.931C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001136273.2(ZFP92):​c.931C>T​(p.Gln311*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000946 in 1,057,310 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 26)
  • Exomes 𝑓: 9.5e-7 (0 hom. 0 hem.)
• Consequence: ZFP92 NM_001136273.2 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00600
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.931C>T	p.Gln311*	stop_gained	Exon 6 of 6	NP_001129745.1	A6NM28
	ZFP92	NM_001386944.1		c.931C>T	p.Gln311*	stop_gained	Exon 5 of 5	NP_001373873.1	A6NM28
	ZFP92	NM_001386945.1		c.931C>T	p.Gln311*	stop_gained	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.931C>T	p.Gln311*	stop_gained	Exon 6 of 6	ENSP00000462054.1	A6NM28
	ZFP92	ENST00000881745.1		c.931C>T	p.Gln311*	stop_gained	Exon 5 of 5	ENSP00000551804.1

Frequencies

GnomAD3 genomes Cov.: 26

GnomAD4 exome AF: 9.46e-7 AC: 1 AN: 1057310 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 343882

African (AFR) AF: 0.00 AC: 0 AN: 25137

American (AMR) AF: 0.00 AC: 0 AN: 29127

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18699

East Asian (EAS) AF: 0.00 AC: 0 AN: 27716

South Asian (SAS) AF: 0.00 AC: 0 AN: 50576

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33565

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

European-Non Finnish (NFE) AF: 0.00000121 AC: 1 AN: 823757

Other (OTH) AF: 0.00 AC: 0 AN: 44649

GnomAD4 genome Cov.: 26

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.61	D
BayesDel_noAF	Pathogenic	0.63
CADD	Pathogenic	36
DANN	Uncertain	1.0
FATHMM_MKL	Uncertain	0.95	D
PhyloP100		-0.0060
Vest4		0.040
GERP RS		3.0
Mutation Taster		=105/95	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

dbSNP: rs2089000466; hg19: chrX-152686766;