Variant 16-4752507-T-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_021646.4(ZNF500):c.1312A>G(p.Thr438Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000197 in 152,158 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 34)

Consequence

ZNF500
NM_021646.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -6.46

Variant links:

Genes affected

ZNF500 (HGNC:23716): (zinc finger protein 500) 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 by RNA polymerase II. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ZNF500 links:

ZNF500 (HGNC:):

ZNF500 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=0.020880431).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF500	NM_021646.4 linkuse as main transcript	c.1312A>G	p.Thr438Ala	missense_variant	6/6	ENST00000219478.11	NP_067678.1	O60304-1
ZNF500	XM_005255243.5 linkuse as main transcript	c.961A>G	p.Thr321Ala	missense_variant	5/5		XP_005255300.1
ZNF500	NM_001303450.2 linkuse as main transcript	c.1297+15A>G		intron_variant			NP_001290379.1	O60304-2
ZNF500	XM_011522453.3 linkuse as main transcript	c.1297+15A>G		intron_variant			XP_011520755.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF500	ENST00000219478.11 linkuse as main transcript	c.1312A>G	p.Thr438Ala	missense_variant	6/6	2	NM_021646.4	ENSP00000219478.5		O60304-1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152040

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

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:

0.0000197

AC:

AN:

152158

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000302

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 30, 2022

The c.1312A>G (p.T438A) alteration is located in exon 6 (coding exon 5) of the ZNF500 gene. This alteration results from a A to G substitution at nucleotide position 1312, causing the threonine (T) at amino acid position 438 to be replaced by an alanine (A). 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

0.10

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.66

DANN

Benign

0.64

DEOGEN2

Benign

0.018

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.035

LIST_S2

Benign

0.30

M_CAP

Benign

0.0041

MetaRNN

Benign

0.021

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.26

PrimateAI

Benign

0.46

PROVEAN

Benign

-0.070

REVEL

Benign

0.012

Sift

Benign

0.23

Sift4G

Benign

0.74

Polyphen

0.0040

Vest4

0.015

MutPred

0.28

Loss of phosphorylation at T438 (P = 0.0247);

MVP

0.076

MPC

0.038

ClinPred

0.17

GERP RS

-3.4

Varity_R

0.035

gMVP

0.046

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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