3-138080449-A-T

Variant names:

• chr3-138080449-A-T
• rs384828
• NM_173543.3:c.1288+118T>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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 Gene-Disease associations (from GenCC):

• autosomal recessive polycystic kidney disease

  Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
• polycystic kidney disease 5

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173543.3. 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
	DZIP1L	NM_173543.3	MANE Select	c.1288+118T>A		intron	N/A	NP_775814.2
	DZIP1L	NM_001170538.1		c.1288+118T>A		intron	N/A	NP_001164009.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DZIP1L	ENST00000327532.7	TSL:1 MANE Select	c.1288+118T>A		intron	N/A	ENSP00000332148.2
	DZIP1L	ENST00000466301.1	TSL:3	n.268T>A		non_coding_transcript_exon	Exon 2 of 2
	DZIP1L	ENST00000469243.5	TSL:2	c.1288+118T>A		intron	N/A	ENSP00000419486.1

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

African (AFR) AF: 0.550 AC: 12261 AN: 22278

American (AMR) AF: 0.649 AC: 23964 AN: 36926

Ashkenazi Jewish (ASJ) AF: 0.738 AC: 14240 AN: 19306

East Asian (EAS) AF: 0.613 AC: 21906 AN: 35732

South Asian (SAS) AF: 0.669 AC: 44265 AN: 66150

European-Finnish (FIN) AF: 0.605 AC: 29668 AN: 49072

Middle Eastern (MID) AF: 0.657 AC: 2725 AN: 4148

European-Non Finnish (NFE) AF: 0.717 AC: 462478 AN: 644762

Other (OTH) AF: 0.687 AC: 28363 AN: 41296

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

African (AFR) AF: 0.546 AC: 22646 AN: 41468

American (AMR) AF: 0.694 AC: 10620 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.744 AC: 2580 AN: 3468

East Asian (EAS) AF: 0.630 AC: 3253 AN: 5166

South Asian (SAS) AF: 0.665 AC: 3200 AN: 4814

European-Finnish (FIN) AF: 0.601 AC: 6344 AN: 10560

Middle Eastern (MID) AF: 0.670 AC: 197 AN: 294

European-Non Finnish (NFE) AF: 0.703 AC: 47817 AN: 67984

Other (OTH) AF: 0.662 AC: 1398 AN: 2112

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

May 11, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	4.6
DANN	Benign	0.58
PhyloP100		-0.026
Mutation Taster		=100/0	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: rs384828; hg19: chr3-137799291;