Genetic Variant ZNF91:p.Trp1166Arg (chr19-23359483-A-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003430.4(ZNF91):c.3496T>A(p.Trp1166Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000745 in 1,611,136 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

ZNF91
NM_003430.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.559

Publications

0 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08120638).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003430.4. 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
	ZNF91	NM_003430.4	MANE Select	c.3496T>A	p.Trp1166Arg	missense	Exon 4 of 4	NP_003421.2	Q05481-1
	ZNF91	NM_001300951.2		c.3400T>A	p.Trp1134Arg	missense	Exon 3 of 3	NP_001287880.1	Q05481-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZNF91	ENST00000300619.12	TSL:1 MANE Select	c.3496T>A	p.Trp1166Arg	missense	Exon 4 of 4	ENSP00000300619.6	Q05481-1
ZNF91	ENST00000909304.1		c.3475T>A	p.Trp1159Arg	missense	Exon 4 of 4	ENSP00000579363.1
ZNF91	ENST00000397082.2	TSL:2	c.3400T>A	p.Trp1134Arg	missense	Exon 3 of 3	ENSP00000380272.2	Q05481-2

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152082

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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:

0.00

GnomAD2 exomes

AF:

0.0000121

AC:

AN:

248712

AF XY:

0.00000741

show subpopulations

Gnomad AFR exome

AF:

0.000130

Gnomad AMR exome

AF:

0.0000290

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:

0.00000343

AC:

AN:

1459054

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

726032

show subpopulations

African (AFR)

AF:

0.0000898

AC:

AN:

33406

American (AMR)

AF:

0.0000224

AC:

AN:

44696

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26102

East Asian (EAS)

AF:

0.00

AC:

AN:

39688

South Asian (SAS)

AF:

0.00

AC:

AN:

86182

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53392

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5752

European-Non Finnish (NFE)

AF:

9.01e-7

AC:

AN:

1109554

Other (OTH)

AF:

0.00

AC:

AN:

60282

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152082

Hom.:

Cov.:

AF XY:

0.0000808

AC XY:

AN XY:

74288

show subpopulations

African (AFR)

AF:

0.000145

AC:

AN:

41436

American (AMR)

AF:

0.0000655

AC:

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5166

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10604

Middle Eastern (MID)

AF:

0.00

AC:

AN:

312

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68006

Other (OTH)

AF:

0.00

AC:

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.604

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000491

ExAC

AF:

0.00000826

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.70

CADD

Benign

7.9

(source)

DANN

Benign

0.27

DEOGEN2

Benign

0.064

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0056

LIST_S2

Benign

0.11

M_CAP

Benign

0.0025

MetaRNN

Benign

0.081

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.3

PhyloP100

-0.56

PrimateAI

Benign

0.45

PROVEAN

Benign

-0.90

REVEL

Benign

0.023

Sift

Benign

0.78

Sift4G

Benign

0.81

Polyphen

0.0020

Vest4

0.17

MutPred

0.47

Gain of disorder (P = 0.0082)

MVP

0.19

MPC

0.35

ClinPred

0.013

Varity_R

0.15

gMVP

0.019

Mutation Taster

=99/1

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over