rs10781533

Variant names:

• chr9-136361157-T-C
• rs10781533
• NM_001080849.3:c.*855A>G

Variant summary

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

The NM_001080849.3(DNLZ):​c.*855A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.534 in 152,198 control chromosomes in the GnomAD database, including 22,150 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 0.53 (22143 hom., cov: 34)
  • Exomes 𝑓: 0.50 (7 hom.)
• Consequence: DNLZ NM_001080849.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.736
• Publications: 12 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.596 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.*855A>G		3_prime_UTR	Exon 3 of 3	NP_001074318.1	Q5SXM8
	DNLZ	NR_073565.2		n.1426A>G		non_coding_transcript_exon	Exon 3 of 3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNLZ	ENST00000371738.4	TSL:1 MANE Select	c.*855A>G		3_prime_UTR	Exon 3 of 3	ENSP00000360803.3	Q5SXM8
	DNLZ	ENST00000371739.3	TSL:5	c.*898A>G		3_prime_UTR	Exon 2 of 2	ENSP00000360804.3	Q5SXM7

Frequencies

GnomAD3 genomes AF: 0.534 AC: 81196 AN: 152022 Hom.: 22125 Cov.: 34

Gnomad AFR AF: 0.426

Gnomad AMI AF: 0.681

Gnomad AMR AF: 0.605

Gnomad ASJ AF: 0.584

Gnomad EAS AF: 0.385

Gnomad SAS AF: 0.412

Gnomad FIN AF: 0.525

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.601

Gnomad OTH AF: 0.541

GnomAD4 exome AF: 0.500 AC: 29 AN: 58 Hom.: 7 Cov.: 0 AF XY: 0.476 AC XY: 20 AN XY: 42

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 1.00 AC: 2 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.479 AC: 23 AN: 48

Other (OTH) AF: 0.500 AC: 4 AN: 8

GnomAD4 genome AF: 0.534 AC: 81264 AN: 152140 Hom.: 22143 Cov.: 34 AF XY: 0.528 AC XY: 39277 AN XY: 74386

African (AFR) AF: 0.426 AC: 17681 AN: 41514

American (AMR) AF: 0.605 AC: 9257 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.584 AC: 2023 AN: 3466

East Asian (EAS) AF: 0.384 AC: 1985 AN: 5170

South Asian (SAS) AF: 0.412 AC: 1990 AN: 4828

European-Finnish (FIN) AF: 0.525 AC: 5559 AN: 10592

Middle Eastern (MID) AF: 0.473 AC: 139 AN: 294

European-Non Finnish (NFE) AF: 0.601 AC: 40863 AN: 67956

Other (OTH) AF: 0.542 AC: 1146 AN: 2114

Alfa AF: 0.583 Hom.: 9970

Bravo AF: 0.535

Asia WGS AF: 0.482 AC: 1675 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.83
DANN	Benign	0.14
PhyloP100		-0.74
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10781533; hg19: chr9-139255609; COSMIC: COSV52518114; COSMIC: COSV52518114;