Variant 19-21727218-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_173531.4(ZNF100):c.1094T>C(p.Ile365Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0011 in 1,613,134 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in Lovd as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00082 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0011 ( 6 hom. )

Consequence

ZNF100
NM_173531.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.37

Variant links:

Genes affected

ZNF100 (HGNC:12880): (zinc finger protein 100) 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, DNA-templated. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF100 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009848535).

BP6

Variant 19-21727218-A-G is Benign according to our data. Variant chr19-21727218-A-G is described in Lovd as [Likely_benign].

BS2

High Homozygotes in GnomAdExome4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF100	NM_173531.4 linkuse as main transcript	c.1094T>C	p.Ile365Thr	missense_variant	5/5	ENST00000358296.11	NP_775802.2	Q8IYN0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF100	ENST00000358296.11 linkuse as main transcript	c.1094T>C	p.Ile365Thr	missense_variant	5/5	1	NM_173531.4	ENSP00000351042.5		Q8IYN0
ZNF100	ENST00000305570.10 linkuse as main transcript	c.902T>C	p.Ile301Thr	missense_variant	4/4	1		ENSP00000445201.3		A0A0A0MTN5

Frequencies

GnomAD3 genomes

AF:

0.000825

AC:

125

AN:

151480

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000291

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00151

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000380

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00125

Gnomad OTH

AF:

0.000480

GnomAD3 exomes

AF:

0.000797

AC:

199

AN:

249548

Hom.:

AF XY:

0.000813

AC XY:

110

AN XY:

135344

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000376

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.000559

Gnomad NFE exome

AF:

0.00149

Gnomad OTH exome

AF:

0.000825

GnomAD4 exome

AF:

0.00113

AC:

1647

AN:

1461534

Hom.:

Cov.:

AF XY:

0.00110

AC XY:

800

AN XY:

727056

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000403

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.000564

Gnomad4 NFE exome

AF:

0.00139

Gnomad4 OTH exome

AF:

0.000712

GnomAD4 genome

AF:

0.000825

AC:

125

AN:

151600

Hom.:

Cov.:

AF XY:

0.000850

AC XY:

AN XY:

74106

show subpopulations

Gnomad4 AFR

AF:

0.000290

Gnomad4 AMR

AF:

0.00151

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000380

Gnomad4 NFE

AF:

0.00125

Gnomad4 OTH

AF:

0.000475

Alfa

AF:

0.00109

Hom.:

Bravo

AF:

0.000752

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.00182

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000931

AC:

ExAC

AF:

0.000840

AC:

102

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00191

EpiControl

AF:

0.00119

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

Oct 01, 2024

The c.1094T>C (p.I365T) alteration is located in exon 5 (coding exon 5) of the ZNF100 gene. This alteration results from a T to C substitution at nucleotide position 1094, causing the isoleucine (I) at amino acid position 365 to be replaced by a threonine (T). 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

0.41

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.74

CADD

Benign

0.14

DANN

Benign

0.42

DEOGEN2

Benign

0.0096

T;.;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.00016

LIST_S2

Benign

0.23

.;.;T

M_CAP

Benign

0.0015

MetaRNN

Benign

0.0098

T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.68

N;.;.

PROVEAN

Benign

-2.0

N;.;.

REVEL

Benign

0.025

Sift

Benign

0.28

T;.;.

Sift4G

Benign

0.099

T;T;T

Polyphen

0.58

P;.;.

Vest4

0.067

MVP

0.076

MPC

0.16

ClinPred

0.042

GERP RS

-1.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.051

gMVP

0.010

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