Variant 19-23360274-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_003430.4(ZNF91):c.2705G>A(p.Arg902Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000659 in 151,750 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 34)

Consequence

ZNF91
NM_003430.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.740

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:

ZNF91 (HGNC:):

ZNF91 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.034964412).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF91	NM_003430.4 linkuse as main transcript	c.2705G>A	p.Arg902Lys	missense_variant	4/4	ENST00000300619.12	NP_003421.2	Q05481-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZNF91	ENST00000300619.12 linkuse as main transcript	c.2705G>A	p.Arg902Lys	missense_variant	4/4	1	NM_003430.4	ENSP00000300619.6	Q05481-1
ZNF91	ENST00000397082.2 linkuse as main transcript	c.2609G>A	p.Arg870Lys	missense_variant	3/3	2		ENSP00000380272.2	Q05481-2
ZNF91	ENST00000599743.5 linkuse as main transcript	c.253+13468G>A		intron_variant		3		ENSP00000468867.1	M0QX31
ZNF91	ENST00000596989.1 linkuse as main transcript	n.370+13468G>A		intron_variant		3

Frequencies

GnomAD3 genomes

AF:

0.00000659

AC:

AN:

151750

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000288

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

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000659

AC:

AN:

151750

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74104

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

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

Nov 11, 2024

The c.2705G>A (p.R902K) alteration is located in exon 4 (coding exon 4) of the ZNF91 gene. This alteration results from a G to A substitution at nucleotide position 2705, causing the arginine (R) at amino acid position 902 to be replaced by a lysine (K). 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

0.087

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.81

CADD

Benign

2.7

DANN

Benign

0.63

DEOGEN2

Benign

0.0024

T;.

Eigen

Benign

-1.8

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.032

LIST_S2

Benign

0.031

T;T

M_CAP

Benign

0.0011

MetaRNN

Benign

0.035

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.96

L;.

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.76

N;N

REVEL

Benign

0.0030

Sift

Benign

0.66

T;T

Sift4G

Benign

0.21

T;T

Polyphen

0.13

B;B

Vest4

0.061

MutPred

0.37

Gain of methylation at R902 (P = 0.0199);.;

MVP

0.16

MPC

0.21

ClinPred

0.030

GERP RS

-2.7

Varity_R

0.040

gMVP

0.013

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