chr9-136362016-C-G

Variant names:

• chr9-136362016-C-G
• rs3812552
• NM_001080849.3:c.533G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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. 13/21 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: 𝑓 0.077 (587 hom., cov: 34)
  • Exomes 𝑓: 0.11 (6906 hom.)
• Consequence: DNLZ NM_001080849.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.473
• Publications: 25 publications found

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]

ENSG00000289701 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

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>C	p.Ser178Thr	missense	Exon 3 of 3	NP_001074318.1
	DNLZ	NR_073565.2		n.567G>C		non_coding_transcript_exon	Exon 3 of 3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNLZ	ENST00000371738.4	TSL:1 MANE Select	c.533G>C	p.Ser178Thr	missense	Exon 3 of 3	ENSP00000360803.3
	ENSG00000289701	ENST00000696169.1		n.*2717G>C		non_coding_transcript_exon	Exon 13 of 13	ENSP00000512460.1
	ENSG00000289701	ENST00000696169.1		n.*2717G>C		3_prime_UTR	Exon 13 of 13	ENSP00000512460.1

Frequencies

GnomAD3 genomes AF: 0.0769 AC: 11706 AN: 152204 Hom.: 584 Cov.: 34

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

GnomAD2 exomes AF: 0.0850 AC: 6186 AN: 72812 AF XY: 0.0841

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 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.: 31 AF XY: 0.106 AC XY: 59194 AN XY: 557858

African (AFR) AF: 0.0142 AC: 347 AN: 24488

American (AMR) AF: 0.101 AC: 1297 AN: 12894

Ashkenazi Jewish (ASJ) AF: 0.0418 AC: 660 AN: 15786

East Asian (EAS) AF: 0.119 AC: 3426 AN: 28818

South Asian (SAS) AF: 0.0640 AC: 2292 AN: 35796

European-Finnish (FIN) AF: 0.0663 AC: 2669 AN: 40242

Middle Eastern (MID) AF: 0.0318 AC: 99 AN: 3114

European-Non Finnish (NFE) AF: 0.114 AC: 109011 AN: 953828

Other (OTH) AF: 0.0908 AC: 4196 AN: 46202

GnomAD4 genome AF: 0.0769 AC: 11710 AN: 152322 Hom.: 587 Cov.: 34 AF XY: 0.0750 AC XY: 5584 AN XY: 74478

African (AFR) AF: 0.0216 AC: 899 AN: 41590

American (AMR) AF: 0.0810 AC: 1239 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0444 AC: 154 AN: 3470

East Asian (EAS) AF: 0.132 AC: 683 AN: 5180

South Asian (SAS) AF: 0.0745 AC: 360 AN: 4832

European-Finnish (FIN) AF: 0.0724 AC: 769 AN: 10618

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.109 AC: 7381 AN: 68012

Other (OTH) AF: 0.0673 AC: 142 AN: 2110

Alfa AF: 0.0920 Hom.: 96

Bravo AF: 0.0770

TwinsUK AF: 0.111 AC: 413

ALSPAC AF: 0.117 AC: 451

ESP6500AA AF: 0.0208 AC: 91

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 v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.71	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	13
DANN	Uncertain	0.99
DEOGEN2	Benign	0.011	T
Eigen	Benign	-0.76
Eigen_PC	Benign	-0.78
FATHMM_MKL	Benign	0.22	N
LIST_S2	Benign	0.39	T
MetaRNN	Benign	0.0021	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		0.47
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.056
Sift	Uncertain	0.025	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.012	B
Vest4		0.028
MPC		0.44
ClinPred		0.010	T
GERP RS		1.4
Varity_R		0.088
gMVP		0.26
Mutation Taster		=90/10	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3812552; hg19: chr9-139256468; COSMIC: COSV52517950; COSMIC: COSV52517950;