Variant 19-21726694-G-C 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_173531.4(ZNF100):c.1618C>G(p.Leu540Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00033 in 1,605,840 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00028 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00034 ( 0 hom. )

Consequence

ZNF100
NM_173531.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.90

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 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=0.03794056).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF100	NM_173531.4 linkuse as main transcript	c.1618C>G	p.Leu540Val	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.1618C>G	p.Leu540Val	missense_variant	5/5	1	NM_173531.4	ENSP00000351042.5		Q8IYN0
ZNF100	ENST00000305570.10 linkuse as main transcript	c.1426C>G	p.Leu476Val	missense_variant	4/4	1		ENSP00000445201.3		A0A0A0MTN5

Frequencies

GnomAD3 genomes

AF:

0.000276

AC:

AN:

152100

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

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:

0.000559

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000211

AC:

AN:

241554

Hom.:

AF XY:

0.000183

AC XY:

AN XY:

131190

show subpopulations

Gnomad AFR exome

AF:

0.000130

Gnomad AMR exome

AF:

0.0000303

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:

0.000426

Gnomad OTH exome

AF:

0.000174

GnomAD4 exome

AF:

0.000336

AC:

488

AN:

1453622

Hom.:

Cov.:

AF XY:

0.000303

AC XY:

219

AN XY:

722870

show subpopulations

Gnomad4 AFR exome

AF:

0.0000605

Gnomad4 AMR exome

AF:

0.0000462

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000236

Gnomad4 FIN exome

AF:

0.0000379

Gnomad4 NFE exome

AF:

0.000412

Gnomad4 OTH exome

AF:

0.000384

GnomAD4 genome

AF:

0.000276

AC:

AN:

152218

Hom.:

Cov.:

AF XY:

0.000296

AC XY:

AN XY:

74410

show subpopulations

Gnomad4 AFR

AF:

0.0000722

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:

0.000559

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000455

Hom.:

Bravo

AF:

0.000264

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000354

AC:

ExAC

AF:

0.000231

AC:

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

Aug 02, 2021

The c.1618C>G (p.L540V) alteration is located in exon 5 (coding exon 5) of the ZNF100 gene. This alteration results from a C to G substitution at nucleotide position 1618, causing the leucine (L) at amino acid position 540 to be replaced by a valine (V). 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

0.068

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.74

CADD

Benign

0.87

DANN

Benign

0.80

DEOGEN2

Benign

0.0020

T;.

Eigen

Benign

-0.79

Eigen_PC

Benign

-0.92

FATHMM_MKL

Benign

0.0095

M_CAP

Benign

0.0014

MetaRNN

Benign

0.038

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.3

L;.

PROVEAN

Benign

-0.12

N;.

REVEL

Benign

0.025

Sift

Benign

0.084

T;.

Sift4G

Uncertain

0.043

D;D

Polyphen

0.020

B;.

Vest4

0.098

MVP

0.092

MPC

0.054

ClinPred

0.014

GERP RS

-0.41

Varity_R

0.043

gMVP

0.014

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