Variant 19-52315867-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PM2

The NM_001297625.2(ZNF480):c.2T>C(p.Met1?) variant causes a start lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 152,080 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)

Consequence

ZNF480
NM_001297625.2 start_lost

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.360

Variant links:

Genes affected

ZNF480 (HGNC:23305): (zinc finger protein 480) 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]

ZNF480 links:

ENSG00000269535 (HGNC:):

ENSG00000269535 links:

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ACMG classification

Classification made for transcript

Verdict is Pathogenic. Variant got 10 ACMG points.

PVS1

Start lost variant, no new inframe start found.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF480	NM_144684.4 linkuse as main transcript	c.233T>C	p.Met78Thr	missense_variant	4/5	ENST00000595962.6	NP_653285.2	Q8WV37-1B7Z8E1
ZNF480	NM_001297625.2 linkuse as main transcript	c.2T>C	p.Met1?	start_lost	3/4		NP_001284554.1	Q8WV37-2
ZNF480	NM_001297624.2 linkuse as main transcript	c.199+1588T>C		intron_variant			NP_001284553.1	Q8WV37F8WEZ9B7Z8E1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF480	ENST00000595962.6 linkuse as main transcript	c.233T>C	p.Met78Thr	missense_variant	4/5	1	NM_144684.4	ENSP00000471754.1		Q8WV37-1
ZNF480	ENST00000468240.6 linkuse as main transcript	n.233T>C		non_coding_transcript_exon_variant	4/6	2		ENSP00000417424.1		Q8WV37-1

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152080

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152080

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74288

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

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

Dec 20, 2021

The c.233T>C (p.M78T) alteration is located in exon 4 (coding exon 3) of the ZNF480 gene. This alteration results from a T to C substitution at nucleotide position 233, causing the methionine (M) at amino acid position 78 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

Benign

0.14

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.81

CADD

Benign

7.3

DANN

Benign

0.68

DEOGEN2

Benign

0.024

T;.;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.014

LIST_S2

Benign

0.0038

T;T;D

M_CAP

Benign

0.0032

MetaRNN

Benign

0.068

T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-0.64

N;.;.

PrimateAI

Benign

0.40

PROVEAN

Benign

-1.6

.;.;N

REVEL

Benign

0.069

Sift

Uncertain

0.0040

.;.;D

Sift4G

Benign

0.26

T;T;D

Polyphen

0.0010

B;.;.

Vest4

0.23

MutPred

0.34

Gain of relative solvent accessibility (P = 0.09);Gain of relative solvent accessibility (P = 0.09);.;

MVP

0.11

MPC

0.059

ClinPred

0.079

GERP RS

-0.65

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.034

gMVP

0.079

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