Variant chr19-23360404-A-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_003430.4(ZNF91):c.2575T>C(p.Cys859Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000762 in 1,613,970 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00019 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000064 ( 0 hom. )

Consequence

ZNF91
NM_003430.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.00

Variant links:

Genes affected

ZNF91 (HGNC:13166): (zinc finger protein 91) The ZNF91 gene encodes a zinc finger protein of the KRAB (Kruppel-associated box) subfamily (Bellefroid et al., 1991, 1993 [PubMed 2023909] [PubMed 8467795]).[supplied by OMIM, May 2010]

ZNF91 links:

Genome browser will be placed here

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=0.107866794).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF91	NM_003430.4 linkuse as main transcript	c.2575T>C	p.Cys859Arg	missense_variant	4/4	ENST00000300619.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF91	ENST00000300619.12 linkuse as main transcript	c.2575T>C	p.Cys859Arg	missense_variant	4/4	1	NM_003430.4	P1	Q05481-1
ZNF91	ENST00000397082.2 linkuse as main transcript	c.2479T>C	p.Cys827Arg	missense_variant	3/3	2			Q05481-2
ZNF91	ENST00000599743.5 linkuse as main transcript	c.253+13338T>C		intron_variant		3
ZNF91	ENST00000596989.1 linkuse as main transcript	n.370+13338T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.000191

AC:

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.0143

Gnomad AMR

AF:

0.0000654

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:

0.000191

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.0000840

AC:

AN:

249932

Hom.:

AF XY:

0.0000811

AC XY:

AN XY:

135574

show subpopulations

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000168

Gnomad OTH exome

AF:

0.000330

GnomAD4 exome

AF:

0.0000643

AC:

AN:

1461798

Hom.:

Cov.:

AF XY:

0.0000674

AC XY:

AN XY:

727196

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.0000224

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:

0.0000710

Gnomad4 OTH exome

AF:

0.000132

GnomAD4 genome

AF:

0.000191

AC:

AN:

152172

Hom.:

Cov.:

AF XY:

0.000242

AC XY:

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000191

Gnomad4 OTH

AF:

0.000956

Alfa

AF:

0.000132

Hom.:

Bravo

AF:

0.000212

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000351

AC:

ExAC

AF:

0.0000908

AC:

EpiCase

AF:

0.000436

EpiControl

AF:

0.000415

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

May 23, 2024

The c.2575T>C (p.C859R) alteration is located in exon 4 (coding exon 4) of the ZNF91 gene. This alteration results from a T to C substitution at nucleotide position 2575, causing the cysteine (C) at amino acid position 859 to be replaced by an arginine (R). 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

Uncertain

0.36

BayesDel_addAF

Uncertain

0.025

BayesDel_noAF

Uncertain

0.060

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.18

T;.

Eigen

Uncertain

0.27

Eigen_PC

Benign

-0.060

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.013

T;T

M_CAP

Benign

0.022

MetaRNN

Benign

0.11

T;T

MetaSVM

Pathogenic

0.85

MutationAssessor

Pathogenic

3.6

H;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.51

PROVEAN

Pathogenic

-8.4

D;D

REVEL

Uncertain

0.51

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0010

D;D

Polyphen

1.0

D;D

Vest4

0.33

MVP

0.96

MPC

0.97

ClinPred

0.82

GERP RS

1.4

Varity_R

0.74

gMVP

0.086

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