rs384828

Positions:

• chr3-138080449-A-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_173543.3(DZIP1L):​c.1288+118T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.689 in 1,071,740 control chromosomes in the GnomAD database, including 256,523 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.65 (32468 hom., cov: 32)
  • Exomes 𝑓: 0.70 (224055 hom.)
• Consequence: DZIP1L NM_173543.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0260

Genes affected

DZIP1L (HGNC:26551): (DAZ interacting zinc finger protein 1 like) Predicted to enable metal ion binding activity. Involved in cilium assembly and regulation of protein localization. Located in ciliary basal body. Colocalizes with centriole. Implicated in polycystic kidney disease 5. [provided by Alliance of Genome Resources, Apr 2022]

DZIP1L (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 3-138080449-A-T is Benign according to our data. Variant chr3-138080449-A-T is described in ClinVar as [Benign]. Clinvar id is 1271645.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.698 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DZIP1L	NM_173543.3	c.1288+118T>A		intron_variant		ENST00000327532.7	NP_775814.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DZIP1L	ENST00000327532.7	c.1288+118T>A		intron_variant		1	NM_173543.3	ENSP00000332148.2
DZIP1L	ENST00000469243.5	c.1288+118T>A		intron_variant		2		ENSP00000419486.1
DZIP1L	ENST00000466301.1	n.268T>A		non_coding_transcript_exon_variant	2/2	3
DZIP1L	ENST00000488595.1	n.360+118T>A		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.649 AC: 98586 AN: 151952 Hom.: 32451 Cov.: 32

Gnomad AFR AF: 0.546

Gnomad AMI AF: 0.657

Gnomad AMR AF: 0.694

Gnomad ASJ AF: 0.744

Gnomad EAS AF: 0.631

Gnomad SAS AF: 0.664

Gnomad FIN AF: 0.601

Gnomad MID AF: 0.665

Gnomad NFE AF: 0.703

Gnomad OTH AF: 0.668

GnomAD4 exome AF: 0.696 AC: 639870 AN: 919670 Hom.: 224055 Cov.: 11 AF XY: 0.695 AC XY: 326257 AN XY: 469176

Gnomad4 AFR exome AF: 0.550

Gnomad4 AMR exome AF: 0.649

Gnomad4 ASJ exome AF: 0.738

Gnomad4 EAS exome AF: 0.613

Gnomad4 SAS exome AF: 0.669

Gnomad4 FIN exome AF: 0.605

Gnomad4 NFE exome AF: 0.717

Gnomad4 OTH exome AF: 0.687

GnomAD4 genome AF: 0.649 AC: 98653 AN: 152070 Hom.: 32468 Cov.: 32 AF XY: 0.645 AC XY: 47961 AN XY: 74336

Gnomad4 AFR AF: 0.546

Gnomad4 AMR AF: 0.694

Gnomad4 ASJ AF: 0.744

Gnomad4 EAS AF: 0.630

Gnomad4 SAS AF: 0.665

Gnomad4 FIN AF: 0.601

Gnomad4 NFE AF: 0.703

Gnomad4 OTH AF: 0.662

Alfa AF: 0.667 Hom.: 4261

Bravo AF: 0.649

Asia WGS AF: 0.611 AC: 2130 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 11, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	4.6
DANN	Benign	0.58

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: rs384828; hg19: chr3-137799291;