3-138063081-A-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate 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, single submitter B:1
• Conservation: PhyloP100: 1.26

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]

ACMG classification

Verdict is Benign. Variant got -14 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 id is 1236019.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.858 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DZIP1L	NM_173543.3	c.2143-104T>G		intron_variant		ENST00000327532.7
DZIP1L	XM_005247198.4	c.2227-104T>G		intron_variant
DZIP1L	XM_047447642.1	c.2086-104T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DZIP1L	ENST00000327532.7	c.2143-104T>G		intron_variant		1	NM_173543.3	P2

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

Gnomad4 AFR exome AF: 0.346

Gnomad4 AMR exome AF: 0.720

Gnomad4 ASJ exome AF: 0.870

Gnomad4 EAS exome AF: 0.620

Gnomad4 SAS exome AF: 0.740

Gnomad4 FIN exome AF: 0.755

Gnomad4 NFE exome AF: 0.871

Gnomad4 OTH exome AF: 0.804

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

Gnomad4 AFR AF: 0.362

Gnomad4 AMR AF: 0.777

Gnomad4 ASJ AF: 0.881

Gnomad4 EAS AF: 0.642

Gnomad4 SAS AF: 0.727

Gnomad4 FIN AF: 0.739

Gnomad4 NFE AF: 0.864

Gnomad4 OTH AF: 0.734

Alfa AF: 0.839 Hom.: 49342

Bravo AF: 0.682

Asia WGS AF: 0.633 AC: 2203 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 11, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	10
Dann	Benign	0.79

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: rs329388; hg19: chr3-137781923; COSMIC: COSV59520401; COSMIC: COSV59520401;