Variant X-153421308-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001136273.2(ZFP92):c.931C>G(p.Gln311Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000881 in 113,467 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000088 ( 0 hom., 0 hem., cov: 26)

Consequence

ZFP92
NM_001136273.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.00600

Variant links:

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]

ZFP92 links:

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ACMG classification

Classification made for transcript

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=0.15048924).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZFP92	NM_001136273.2 linkuse as main transcript	c.931C>G	p.Gln311Glu	missense_variant	6/6	ENST00000338647.7	NP_001129745.1	A6NM28
ZFP92	NM_001386944.1 linkuse as main transcript	c.931C>G	p.Gln311Glu	missense_variant	5/5		NP_001373873.1
ZFP92	NM_001386945.1 linkuse as main transcript	c.931C>G	p.Gln311Glu	missense_variant	7/7		NP_001373874.1
ZFP92	NM_001386943.1 linkuse as main transcript	c.805C>G	p.Gln269Glu	missense_variant	4/4		NP_001373872.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZFP92	ENST00000338647.7 linkuse as main transcript	c.931C>G	p.Gln311Glu	missense_variant	6/6	5	NM_001136273.2	ENSP00000462054.1		A6NM28

Frequencies

GnomAD3 genomes

AF:

0.00000881

AC:

AN:

113467

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

35667

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000648

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000881

AC:

AN:

113467

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

35667

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000648

Bravo

AF:

0.0000227

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 01, 2023

The c.931C>G (p.Q311E) alteration is located in exon 4 (coding exon 4) of the ZFP92 gene. This alteration results from a C to G substitution at nucleotide position 931, causing the glutamine (Q) at amino acid position 311 to be replaced by a glutamic acid (E). 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

0.16

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.76

CADD

Uncertain

DANN

Benign

0.95

DEOGEN2

Benign

0.034

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.33

M_CAP

Uncertain

0.10

MetaRNN

Benign

0.15

MutationAssessor

Benign

0.64

PrimateAI

Uncertain

0.64

Sift4G

Uncertain

0.020

Polyphen

0.55

Vest4

0.13

MVP

0.39

MPC

2.3

GERP RS

3.0

Varity_R

0.19

gMVP

0.86

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over