Variant 15-56654221-G-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_017661.4(ZNF280D):c.2190C>G(p.Ile730Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000686 in 1,458,292 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000069 ( 0 hom. )

Consequence

ZNF280D
NM_017661.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.929

Variant links:

Genes affected

ZNF280D (HGNC:25953): (zinc finger protein 280D) 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]

ZNF280D links:

Genome browser will be placed here

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=0.14018124).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ZNF280D	NM_017661.4 linkuse as main transcript	c.2190C>G	p.Ile730Met	missense_variant	19/22	ENST00000267807.12	NP_060131.2
ZNF280D	NM_001288588.2 linkuse as main transcript	c.2190C>G	p.Ile730Met	missense_variant	19/22		NP_001275517.1
ZNF280D	NM_001002843.3 linkuse as main transcript	c.2151C>G	p.Ile717Met	missense_variant	18/21		NP_001002843.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF280D	ENST00000267807.12 linkuse as main transcript	c.2190C>G	p.Ile730Met	missense_variant	19/22	1	NM_017661.4	ENSP00000267807	P1	Q6N043-1
ZNF280D	ENST00000559237.5 linkuse as main transcript	c.2151C>G	p.Ile717Met	missense_variant	18/21	1		ENSP00000454111		Q6N043-2
ZNF280D	ENST00000558067.5 linkuse as main transcript	c.*148C>G		3_prime_UTR_variant, NMD_transcript_variant	11/14	2		ENSP00000454173		Q6N043-4
ZNF280D	ENST00000560002.5 linkuse as main transcript	c.*440C>G		3_prime_UTR_variant, NMD_transcript_variant	17/17	5		ENSP00000453636		Q6N043-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000404

AC:

AN:

247618

Hom.:

AF XY:

0.00

AC XY:

AN XY:

133610

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.00000889

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000686

AC:

AN:

1458292

Hom.:

Cov.:

AF XY:

0.00000827

AC XY:

AN XY:

725130

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000810

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.00000824

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

Jan 03, 2024

The c.2190C>G (p.I730M) alteration is located in exon 19 (coding exon 17) of the ZNF280D gene. This alteration results from a C to G substitution at nucleotide position 2190, causing the isoleucine (I) at amino acid position 730 to be replaced by a methionine (M). 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

0.095

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.040

.;T

Eigen

Benign

-0.040

Eigen_PC

Benign

0.036

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.74

T;T

M_CAP

Benign

0.018

MetaRNN

Benign

0.14

T;T

MetaSVM

Benign

-0.78

MutationAssessor

Uncertain

2.1

.;M

MutationTaster

Benign

1.0

D;N;N

PrimateAI

Benign

0.44

PROVEAN

Benign

-0.25

.;N

REVEL

Benign

0.055

Sift

Benign

0.058

.;T

Sift4G

Benign

0.17

T;T

Polyphen

0.89

.;P

Vest4

0.21

MutPred

0.36

.;Gain of disorder (P = 0.0209);

MVP

0.34

MPC

0.89

ClinPred

0.25

GERP RS

4.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.064

gMVP

0.15

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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