Genetic Variant NM_014487.6:c.819T>G (chr4-141233845-T-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_014487.6(ZNF330):c.819T>G(p.Asp273Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,461,482 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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: 0.0000041 ( 0 hom. )

Consequence

ZNF330
NM_014487.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.246

Publications

0 publications found

Variant links:

Genes affected

ZNF330 (HGNC:15462): (zinc finger protein 330) Predicted to enable zinc ion binding activity. Located in chromosome, centromeric region; midbody; and nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF330 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.029919267).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014487.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF330	NM_014487.6	MANE Select	c.819T>G	p.Asp273Glu	missense	Exon 10 of 10	NP_055302.1	Q9Y3S2
	ZNF330	NM_001292002.2		c.639T>G	p.Asp213Glu	missense	Exon 9 of 9	NP_001278931.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZNF330	ENST00000262990.9	TSL:1 MANE Select	c.819T>G	p.Asp273Glu	missense	Exon 10 of 10	ENSP00000262990.4	Q9Y3S2
ZNF330	ENST00000955956.1		c.819T>G	p.Asp273Glu	missense	Exon 10 of 10	ENSP00000626015.1
ZNF330	ENST00000955957.1		c.819T>G	p.Asp273Glu	missense	Exon 10 of 10	ENSP00000626016.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000120

AC:

AN:

249680

AF XY:

0.0000222

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000891

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000411

AC:

AN:

1461482

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

727046

show subpopulations

African (AFR)

AF:

0.0000598

AC:

AN:

33460

American (AMR)

AF:

0.00

AC:

AN:

44658

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26124

East Asian (EAS)

AF:

0.00

AC:

AN:

39694

South Asian (SAS)

AF:

0.0000348

AC:

AN:

86246

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53396

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111778

Other (OTH)

AF:

0.00

AC:

AN:

60358

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.62

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0054

Eigen

Benign

-0.71

Eigen_PC

Benign

-0.58

FATHMM_MKL

Benign

0.41

LIST_S2

Benign

0.50

M_CAP

Benign

0.0025

MetaRNN

Benign

0.030

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.5

PhyloP100

-0.25

PrimateAI

Benign

0.40

PROVEAN

Benign

-1.0

REVEL

Benign

0.016

Sift

Benign

0.54

Sift4G

Benign

0.096

Polyphen

0.0

Vest4

0.11

MutPred

0.38

Loss of loop (P = 0.0603)

MVP

0.17

MPC

0.18

ClinPred

0.13

GERP RS

-0.47

Varity_R

0.032

gMVP

0.019

Mutation Taster

=75/25

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over