Variant rs3812552 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001080849.3(DNLZ):c.533G>C(p.Ser178Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 1,313,490 control chromosomes in the GnomAD database, including 7,493 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.077 ( 587 hom., cov: 34)

Exomes 𝑓: 0.11 ( 6906 hom. )

Consequence

DNLZ
NM_001080849.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.473

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002127558).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.124 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNLZ	NM_001080849.3 linkuse as main transcript	c.533G>C	p.Ser178Thr	missense_variant	3/3	ENST00000371738.4	NP_001074318.1	Q5SXM8
DNLZ	NR_073565.2 linkuse as main transcript	n.567G>C		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DNLZ	ENST00000371738.4 linkuse as main transcript	c.533G>C	p.Ser178Thr	missense_variant	3/3	1	NM_001080849.3	ENSP00000360803.3	Q5SXM8
ENSG00000289701	ENST00000696169.1 linkuse as main transcript	n.*2717G>C		non_coding_transcript_exon_variant	13/13			ENSP00000512460.1
ENSG00000289701	ENST00000696169.1 linkuse as main transcript	n.*2717G>C		3_prime_UTR_variant	13/13			ENSP00000512460.1
DNLZ	ENST00000371739 linkuse as main transcript	c.*39G>C		3_prime_UTR_variant	2/2	5		ENSP00000360804.3	Q5SXM7

Frequencies

GnomAD3 genomes

AF:

0.0769

AC:

11706

AN:

152204

Hom.:

584

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0217

Gnomad AMI

AF:

0.0811

Gnomad AMR

AF:

0.0809

Gnomad ASJ

AF:

0.0444

Gnomad EAS

AF:

0.132

Gnomad SAS

AF:

0.0740

Gnomad FIN

AF:

0.0724

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.108

Gnomad OTH

AF:

0.0680

GnomAD3 exomes

AF:

0.0850

AC:

6186

AN:

72812

Hom.:

274

AF XY:

0.0841

AC XY:

3293

AN XY:

39148

show subpopulations

Gnomad AFR exome

AF:

0.0179

Gnomad AMR exome

AF:

0.0981

Gnomad ASJ exome

AF:

0.0453

Gnomad EAS exome

AF:

0.120

Gnomad SAS exome

AF:

0.0674

Gnomad FIN exome

AF:

0.0647

Gnomad NFE exome

AF:

0.100

Gnomad OTH exome

AF:

0.0770

GnomAD4 exome

AF:

0.107

AC:

123997

AN:

1161168

Hom.:

6906

Cov.:

AF XY:

0.106

AC XY:

59194

AN XY:

557858

show subpopulations

Gnomad4 AFR exome

AF:

0.0142

Gnomad4 AMR exome

AF:

0.101

Gnomad4 ASJ exome

AF:

0.0418

Gnomad4 EAS exome

AF:

0.119

Gnomad4 SAS exome

AF:

0.0640

Gnomad4 FIN exome

AF:

0.0663

Gnomad4 NFE exome

AF:

0.114

Gnomad4 OTH exome

AF:

0.0908

GnomAD4 genome

AF:

0.0769

AC:

11710

AN:

152322

Hom.:

587

Cov.:

AF XY:

0.0750

AC XY:

5584

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.0216

Gnomad4 AMR

AF:

0.0810

Gnomad4 ASJ

AF:

0.0444

Gnomad4 EAS

AF:

0.132

Gnomad4 SAS

AF:

0.0745

Gnomad4 FIN

AF:

0.0724

Gnomad4 NFE

AF:

0.109

Gnomad4 OTH

AF:

0.0673

Alfa

AF:

0.0920

Hom.:

Bravo

AF:

0.0770

TwinsUK

AF:

0.111

AC:

413

ALSPAC

AF:

0.117

AC:

451

ESP6500AA

AF:

0.0208

AC:

ESP6500EA

AF:

0.103

AC:

879

ExAC

AF:

0.0703

AC:

8359

Asia WGS

AF:

0.119

AC:

414

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.69

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.011

Eigen

Benign

-0.76

Eigen_PC

Benign

-0.78

FATHMM_MKL

Benign

0.22

LIST_S2

Benign

0.39

MetaRNN

Benign

0.0021

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.1

PrimateAI

Benign

0.45

PROVEAN

Benign

-1.0

REVEL

Benign

0.056

Sift

Uncertain

0.025

Sift4G

Pathogenic

0.0

Polyphen

0.012

Vest4

0.028

MPC

0.44

ClinPred

0.010

GERP RS

1.4

Varity_R

0.088

gMVP

0.26

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over