NM_001136273.2:c.233C>T

Variant names:

• chrX-153420300-C-T
• rs1556974668
• NM_001136273.2:c.233C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001136273.2(ZFP92):​c.233C>T​(p.Pro78Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000038 in 1,053,792 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. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 0.0000038 (0 hom. 1 hem.)
• Consequence: ZFP92 NM_001136273.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.82
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.035841405).

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.233C>T	p.Pro78Leu	missense	Exon 5 of 6	NP_001129745.1	A6NM28
	ZFP92	NM_001386944.1		c.233C>T	p.Pro78Leu	missense	Exon 4 of 5	NP_001373873.1	A6NM28
	ZFP92	NM_001386945.1		c.233C>T	p.Pro78Leu	missense	Exon 6 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.233C>T	p.Pro78Leu	missense	Exon 5 of 6	ENSP00000462054.1	A6NM28
	ZFP92	ENST00000881745.1		c.233C>T	p.Pro78Leu	missense	Exon 4 of 5	ENSP00000551804.1

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD2 exomes AF: 0.0000263 AC: 3 AN: 114157 AF XY: 0.0000247

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000380 AC: 4 AN: 1053792 Hom.: 0 Cov.: 30 AF XY: 0.00000290 AC XY: 1 AN XY: 344562

African (AFR) AF: 0.00 AC: 0 AN: 24900

American (AMR) AF: 0.00 AC: 0 AN: 27858

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18624

East Asian (EAS) AF: 0.0000369 AC: 1 AN: 27111

South Asian (SAS) AF: 0.0000602 AC: 3 AN: 49801

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37668

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4082

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 819370

Other (OTH) AF: 0.00 AC: 0 AN: 44378

GnomAD4 genome Cov.: 24

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	Benign	0.20
BayesDel_addAF	Benign	-0.85	T
BayesDel_noAF	Benign	-1.2
CADD	Benign	0.0040
DANN	Benign	0.84
DEOGEN2	Benign	0.038	T
FATHMM_MKL	Benign	0.0014	N
LIST_S2	Benign	0.24	T
M_CAP	Benign	0.0027	T
MetaRNN	Benign	0.036	T
MutationAssessor	Benign	0.12	N
PhyloP100		-1.8
PrimateAI	Benign	0.24	T
Sift4G	Benign	0.14	T
Polyphen		0.0	B
Vest4		0.054
MVP		0.068
MPC		1.0
GERP RS		-5.3
Varity_R		0.033
gMVP		0.21
Mutation Taster		=100/0	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: rs1556974668; hg19: chrX-152685758;