dbSNP rs3829109: DNLZ:c.369-134C>T (chr9-136362314-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001080849.3(DNLZ):c.369-134C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.256 in 759,736 control chromosomes in the GnomAD database, including 26,258 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.24 ( 5016 hom., cov: 34)

Exomes 𝑓: 0.26 ( 21242 hom. )

Consequence

DNLZ
NM_001080849.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.392

Publications

53 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.336 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNLZ	NM_001080849.3	MANE Select	c.369-134C>T		intron	N/A	NP_001074318.1	Q5SXM8
	DNLZ	NR_073565.2		n.403-134C>T		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DNLZ	ENST00000371738.4	TSL:1 MANE Select	c.369-134C>T	intron	N/A	ENSP00000360803.3	Q5SXM8
ENSG00000289701	ENST00000696169.1		n.*2553-134C>T	intron	N/A	ENSP00000512460.1
DNLZ	ENST00000893401.1		c.369-44C>T	intron	N/A	ENSP00000563460.1

Frequencies

GnomAD3 genomes

AF:

0.244

AC:

37077

AN:

151992

Hom.:

5010

Cov.:

show subpopulations

Gnomad AFR

AF:

0.169

Gnomad AMI

AF:

0.258

Gnomad AMR

AF:

0.343

Gnomad ASJ

AF:

0.200

Gnomad EAS

AF:

0.0551

Gnomad SAS

AF:

0.204

Gnomad FIN

AF:

0.345

Gnomad MID

AF:

0.149

Gnomad NFE

AF:

0.272

Gnomad OTH

AF:

0.234

GnomAD4 exome

AF:

0.259

AC:

157164

AN:

607626

Hom.:

21242

AF XY:

0.257

AC XY:

76922

AN XY:

299738

show subpopulations

African (AFR)

AF:

0.163

AC:

2299

AN:

14106

American (AMR)

AF:

0.388

AC:

3277

AN:

8448

Ashkenazi Jewish (ASJ)

AF:

0.206

AC:

2433

AN:

11798

East Asian (EAS)

AF:

0.111

AC:

2767

AN:

24848

South Asian (SAS)

AF:

0.207

AC:

4025

AN:

19458

European-Finnish (FIN)

AF:

0.352

AC:

8922

AN:

25346

Middle Eastern (MID)

AF:

0.180

AC:

376

AN:

2084

European-Non Finnish (NFE)

AF:

0.267

AC:

126277

AN:

473144

Other (OTH)

AF:

0.239

AC:

6788

AN:

28394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

5835

11670

17506

23341

29176

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3768

7536

11304

15072

18840

<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

AF:

0.244

AC:

37098

AN:

152110

Hom.:

5016

Cov.:

AF XY:

0.246

AC XY:

18258

AN XY:

74362

show subpopulations

African (AFR)

AF:

0.168

AC:

6983

AN:

41510

American (AMR)

AF:

0.344

AC:

5251

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.200

AC:

692

AN:

3468

East Asian (EAS)

AF:

0.0550

AC:

285

AN:

5182

South Asian (SAS)

AF:

0.204

AC:

984

AN:

4830

European-Finnish (FIN)

AF:

0.345

AC:

3651

AN:

10576

Middle Eastern (MID)

AF:

0.160

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.272

AC:

18478

AN:

67948

Other (OTH)

AF:

0.233

AC:

492

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

1375

2750

4126

5501

6876

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

380

760

1140

1520

1900

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.262

Hom.:

9006

Bravo

AF:

0.238

Asia WGS

AF:

0.150

AC:

522

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.44

(source)

DANN

Benign

0.68

PhyloP100

-0.39

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over