rs329388

Variant names:

• chr3-138063081-A-C
• rs329388
• NM_173543.3:c.2143-104T>G

Your query was ambiguous. Multiple possible variants found:

• chr3-138063081-A-C
• chr3-138063081-A-G

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.2143-104T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.816 in 1,301,224 control chromosomes in the GnomAD database, including 443,627 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.70 (40413 hom., cov: 31)
  • Exomes 𝑓: 0.83 (403214 hom.)
• Consequence: DZIP1L NM_173543.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.26
• Publications: 0 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: ClinGen, Orphanet
• 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=-0.81).
• BP6: Variant 3-138063081-A-C is Benign according to our data. Variant chr3-138063081-A-C is described in ClinVar as Benign. ClinVar VariationId is 1236019.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.858 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DZIP1L	NM_173543.3	MANE Select	c.2143-104T>G		intron	N/A	NP_775814.2	Q8IYY4-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DZIP1L	ENST00000327532.7	TSL:1 MANE Select	c.2143-104T>G		intron	N/A	ENSP00000332148.2	Q8IYY4-1
	DZIP1L	ENST00000851674.1		c.2143-104T>G		intron	N/A	ENSP00000521733.1
	DZIP1L	ENST00000912002.1		c.2143-104T>G		intron	N/A	ENSP00000582061.1

Frequencies

GnomAD3 genomes AF: 0.697 AC: 105841 AN: 151866 Hom.: 40417 Cov.: 31

Gnomad AFR AF: 0.362

Gnomad AMI AF: 0.841

Gnomad AMR AF: 0.777

Gnomad ASJ AF: 0.881

Gnomad EAS AF: 0.643

Gnomad SAS AF: 0.725

Gnomad FIN AF: 0.739

Gnomad MID AF: 0.829

Gnomad NFE AF: 0.864

Gnomad OTH AF: 0.742

GnomAD4 exome AF: 0.831 AC: 955492 AN: 1149238 Hom.: 403214 AF XY: 0.831 AC XY: 476534 AN XY: 573572

African (AFR) AF: 0.346 AC: 9474 AN: 27352

American (AMR) AF: 0.720 AC: 25322 AN: 35156

Ashkenazi Jewish (ASJ) AF: 0.870 AC: 18125 AN: 20826

East Asian (EAS) AF: 0.620 AC: 23041 AN: 37156

South Asian (SAS) AF: 0.740 AC: 51178 AN: 69186

European-Finnish (FIN) AF: 0.755 AC: 27137 AN: 35926

Middle Eastern (MID) AF: 0.799 AC: 2830 AN: 3544

European-Non Finnish (NFE) AF: 0.871 AC: 758427 AN: 870416

Other (OTH) AF: 0.804 AC: 39958 AN: 49676

GnomAD4 genome AF: 0.697 AC: 105867 AN: 151986 Hom.: 40413 Cov.: 31 AF XY: 0.694 AC XY: 51520 AN XY: 74262

African (AFR) AF: 0.362 AC: 15008 AN: 41420

American (AMR) AF: 0.777 AC: 11887 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.881 AC: 3059 AN: 3472

East Asian (EAS) AF: 0.642 AC: 3305 AN: 5148

South Asian (SAS) AF: 0.727 AC: 3492 AN: 4804

European-Finnish (FIN) AF: 0.739 AC: 7800 AN: 10556

Middle Eastern (MID) AF: 0.827 AC: 243 AN: 294

European-Non Finnish (NFE) AF: 0.864 AC: 58757 AN: 67978

Other (OTH) AF: 0.734 AC: 1551 AN: 2112

Alfa AF: 0.814 Hom.: 62979

Bravo AF: 0.682

Asia WGS AF: 0.633 AC: 2203 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	10
DANN	Benign	0.79
PhyloP100		1.3
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: rs329388; hg19: chr3-137781923; COSMIC: COSV59520401; COSMIC: COSV59520401;