Genetic Variant NM_001080849.3:c.533G>A (chr9-136362016-C-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001080849.3(DNLZ):c.533G>A(p.Ser178Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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.

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

DNLZ
NM_001080849.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.473

Publications

25 publications found

Variant links:

Genes affected

DNLZ (HGNC:33879): (DNL-type zinc finger) Predicted to enable chaperone binding activity. Predicted to be involved in protein folding; protein import into mitochondrial matrix; and protein stabilization. Located in mitochondrion and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

DNLZ links:

ENSG00000289701 (HGNC:):

ENSG00000289701 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3778001).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080849.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNLZ	NM_001080849.3	MANE Select	c.533G>A	p.Ser178Asn	missense	Exon 3 of 3	NP_001074318.1
	DNLZ	NR_073565.2		n.567G>A		non_coding_transcript_exon	Exon 3 of 3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
DNLZ	ENST00000371738.4	TSL:1 MANE Select	c.533G>A	p.Ser178Asn	missense	Exon 3 of 3	ENSP00000360803.3
ENSG00000289701	ENST00000696169.1		n.*2717G>A		non_coding_transcript_exon	Exon 13 of 13	ENSP00000512460.1
ENSG00000289701	ENST00000696169.1		n.*2717G>A		3_prime_UTR	Exon 13 of 13	ENSP00000512460.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

72812

AF XY:

0.00

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1161616

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

558078

African (AFR)

AF:

0.00

AC:

AN:

24488

American (AMR)

AF:

0.00

AC:

AN:

12910

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

15792

East Asian (EAS)

AF:

0.00

AC:

AN:

28826

South Asian (SAS)

AF:

0.00

AC:

AN:

35838

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40268

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3114

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

954174

Other (OTH)

AF:

0.00

AC:

AN:

46206

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000841

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.65

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0046

Eigen

Benign

-0.62

Eigen_PC

Benign

-0.68

FATHMM_MKL

Benign

0.47

LIST_S2

Benign

0.46

M_CAP

Benign

0.018

MetaRNN

Benign

0.38

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.1

PhyloP100

0.47

PrimateAI

Benign

0.47

PROVEAN

Benign

-1.0

REVEL

Benign

0.030

Sift

Benign

0.081

Sift4G

Pathogenic

0.0

Polyphen

0.42

Vest4

0.12

MVP

0.014

MPC

0.51

ClinPred

0.37

GERP RS

1.4

Varity_R

0.059

gMVP

0.22

Mutation Taster

=92/8

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over