rs10870149

Variant names:

• chr9-136360445-G-A
• rs10870149
• NM_001080849.3:c.*1567C>T

Variant summary

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

The NM_001080849.3(DNLZ):​c.*1567C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.459 in 152,004 control chromosomes in the GnomAD database, including 16,298 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 0.46 (16284 hom., cov: 32)
  • Exomes 𝑓: 0.52 (14 hom.)
• Consequence: DNLZ NM_001080849.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.61
• Publications: 23 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.535 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNLZ	NM_001080849.3	c.*1567C>T		3_prime_UTR_variant	Exon 3 of 3	ENST00000371738.4	NP_001074318.1
DNLZ	NR_073565.2	n.2138C>T		non_coding_transcript_exon_variant	Exon 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNLZ	ENST00000371738.4	c.*1567C>T		3_prime_UTR_variant	Exon 3 of 3	1	NM_001080849.3	ENSP00000360803.3
DNLZ	ENST00000371739.3	c.*1610C>T		3_prime_UTR_variant	Exon 2 of 2	5		ENSP00000360804.3

Frequencies

GnomAD3 genomes AF: 0.459 AC: 69652 AN: 151804 Hom.: 16265 Cov.: 32

Gnomad AFR AF: 0.376

Gnomad AMI AF: 0.599

Gnomad AMR AF: 0.544

Gnomad ASJ AF: 0.503

Gnomad EAS AF: 0.325

Gnomad SAS AF: 0.369

Gnomad FIN AF: 0.488

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.499

Gnomad OTH AF: 0.462

GnomAD4 exome AF: 0.524 AC: 43 AN: 82 Hom.: 14 Cov.: 0 AF XY: 0.440 AC XY: 22 AN XY: 50

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AF: 0.250 AC: 1 AN: 4

European-Finnish (FIN) AF: 0.450 AC: 9 AN: 20

Middle Eastern (MID) AF: 1.00 AC: 2 AN: 2

European-Non Finnish (NFE) AF: 0.643 AC: 27 AN: 42

Other (OTH) AF: 0.400 AC: 4 AN: 10

GnomAD4 genome AF: 0.459 AC: 69723 AN: 151922 Hom.: 16284 Cov.: 32 AF XY: 0.456 AC XY: 33875 AN XY: 74252

African (AFR) AF: 0.376 AC: 15590 AN: 41430

American (AMR) AF: 0.544 AC: 8317 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.503 AC: 1743 AN: 3466

East Asian (EAS) AF: 0.324 AC: 1660 AN: 5126

South Asian (SAS) AF: 0.369 AC: 1780 AN: 4820

European-Finnish (FIN) AF: 0.488 AC: 5143 AN: 10548

Middle Eastern (MID) AF: 0.337 AC: 99 AN: 294

European-Non Finnish (NFE) AF: 0.498 AC: 33870 AN: 67944

Other (OTH) AF: 0.463 AC: 975 AN: 2106

Alfa AF: 0.471 Hom.: 12534

Bravo AF: 0.459

Asia WGS AF: 0.415 AC: 1445 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.030
DANN	Benign	0.44
PhyloP100		-2.6
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: rs10870149; hg19: chr9-139254897;