Variant chr19-21727320-T-C 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_173531.4(ZNF100):c.992A>G(p.His331Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000133 in 150,864 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 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 0.000013 ( 0 hom., cov: 33)

Consequence

ZNF100
NM_173531.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -3.10

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:

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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=0.2216754).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF100	NM_173531.4 linkuse as main transcript	c.992A>G	p.His331Arg	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.992A>G	p.His331Arg	missense_variant	5/5	1	NM_173531.4	ENSP00000351042.5		Q8IYN0
ZNF100	ENST00000305570.10 linkuse as main transcript	c.800A>G	p.His267Arg	missense_variant	4/4	1		ENSP00000445201.3		A0A0A0MTN5

Frequencies

GnomAD3 genomes

AF:

0.0000133

AC:

AN:

150864

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000487

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:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.0000133

AC:

AN:

150864

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73688

show subpopulations

Gnomad4 AFR

AF:

0.0000487

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:

0.00

Bravo

AF:

0.00000756

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

Sep 05, 2024

The c.992A>G (p.H331R) alteration is located in exon 5 (coding exon 5) of the ZNF100 gene. This alteration results from a A to G substitution at nucleotide position 992, causing the histidine (H) at amino acid position 331 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

0.52

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.032

DANN

Benign

0.23

DEOGEN2

Benign

0.0045

T;.;.

Eigen

Benign

-0.96

Eigen_PC

Benign

-0.99

FATHMM_MKL

Benign

0.00010

LIST_S2

Benign

0.095

.;.;T

M_CAP

Benign

0.00098

MetaRNN

Benign

0.22

T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.5

L;.;.

PROVEAN

Benign

-1.5

N;.;.

REVEL

Benign

0.023

Sift

Benign

0.37

T;.;.

Sift4G

Benign

0.55

T;T;T

Polyphen

0.053

B;.;.

Vest4

0.063

MutPred

0.27

Gain of MoRF binding (P = 0.0087);.;.;

MVP

0.17

MPC

0.067

ClinPred

0.056

GERP RS

0.84

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.023

gMVP

0.023

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