rs3812552

chr9-136362016-C-Gchr9-136362016-C-T

Variant summary

Our verdict is Benign. Variant got -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. 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.473

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]

ACMG classification

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	UniProt
DNLZ	NM_001080849.3	c.533G>C	p.Ser178Thr	missense_variant	3/3	ENST00000371738.4
DNLZ	NR_073565.2	n.567G>C		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNLZ	ENST00000371738.4	c.533G>C	p.Ser178Thr	missense_variant	3/3	1	NM_001080849.3	P1
DNLZ	ENST00000371739.3	c.*39G>C		3_prime_UTR_variant	2/2	5

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

GnomAD3 exomes AF: 0.0850 AC: 6186 AN: 72812 Hom.: 274 AF XY: 0.0841 AC XY: 3293 AN XY: 39148

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

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.: 34 AF XY: 0.0750 AC XY: 5584 AN XY: 74478

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.: 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 v4.3

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
MutationTaster	Benign	1.0	P;P
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

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

Other links and lift over

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