Genetic Variant NM_014487.6:c.901A>G (chr4-141233927-A-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014487.6(ZNF330):c.901A>G(p.Asn301Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,510 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N301Y) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ZNF330
NM_014487.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.56

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: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13827065).

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.901A>G	p.Asn301Asp	missense	Exon 10 of 10	NP_055302.1	Q9Y3S2
	ZNF330	NM_001292002.2		c.721A>G	p.Asn241Asp	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.901A>G	p.Asn301Asp	missense	Exon 10 of 10	ENSP00000262990.4	Q9Y3S2
ZNF330	ENST00000955956.1		c.901A>G	p.Asn301Asp	missense	Exon 10 of 10	ENSP00000626015.1
ZNF330	ENST00000955957.1		c.901A>G	p.Asn301Asp	missense	Exon 10 of 10	ENSP00000626016.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461510

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727082

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33454

American (AMR)

AF:

0.00

AC:

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26112

East Asian (EAS)

AF:

0.00

AC:

AN:

39694

South Asian (SAS)

AF:

0.00

AC:

AN:

86238

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111742

Other (OTH)

AF:

0.00

AC:

AN:

60378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.59

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0039

Eigen

Benign

-0.15

Eigen_PC

Benign

0.048

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.76

M_CAP

Benign

0.0030

MetaRNN

Benign

0.14

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

PhyloP100

3.6

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-0.21

REVEL

Benign

0.062

Sift

Benign

0.16

Sift4G

Benign

0.32

Polyphen

0.017

Vest4

0.079

MutPred

0.61

Gain of relative solvent accessibility (P = 0.09)

MVP

0.15

MPC

0.27

ClinPred

0.37

GERP RS

5.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.10

gMVP

0.053

Mutation Taster

=94/6

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over