3-138062926-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 2P and 17B. PM2 BP4_Strong BP6_Very_Strong BP7 BS1

The NM_173543.3(DZIP1L):c.2194C>T(p.Leu732=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000916 in 1,614,188 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00061 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00095 (1 hom.)
• Consequence: DZIP1L NM_173543.3 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.42

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 -15 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 3-138062926-G-A is Benign according to our data. Variant chr3-138062926-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1462795.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.42 with no splicing effect.
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.000611 (93/152314) while in subpopulation AMR AF= 0.00111 (17/15298). AF 95% confidence interval is 0.000768. There are 0 homozygotes in gnomad4. There are 38 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DZIP1L	NM_173543.3	c.2194C>T	p.Leu732=	synonymous_variant	16/16	ENST00000327532.7
DZIP1L	XM_005247198.4	c.2278C>T	p.Leu760=	synonymous_variant	16/16
DZIP1L	XM_047447642.1	c.2137C>T	p.Leu713=	synonymous_variant	15/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DZIP1L	ENST00000327532.7	c.2194C>T	p.Leu732=	synonymous_variant	16/16	1	NM_173543.3	P2

Frequencies

GnomAD3 genomes AF: 0.000611 AC: 93 AN: 152196 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00111

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000955

Gnomad OTH AF: 0.000955

GnomAD3 exomes AF: 0.000589 AC: 148 AN: 251454 Hom.: 0 AF XY: 0.000567 AC XY: 77 AN XY: 135910

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.000520

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000555

Gnomad FIN exome AF: 0.0000925

Gnomad NFE exome AF: 0.000914

Gnomad OTH exome AF: 0.000814

GnomAD4 exome AF: 0.000948 AC: 1386 AN: 1461874 Hom.: 1 Cov.: 31 AF XY: 0.000953 AC XY: 693 AN XY: 727240

Gnomad4 AFR exome AF: 0.000149

Gnomad4 AMR exome AF: 0.000358

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000661

Gnomad4 FIN exome AF: 0.000150

Gnomad4 NFE exome AF: 0.00112

Gnomad4 OTH exome AF: 0.000811

GnomAD4 genome AF: 0.000611 AC: 93 AN: 152314 Hom.: 0 Cov.: 32 AF XY: 0.000510 AC XY: 38 AN XY: 74494

Gnomad4 AFR AF: 0.000144

Gnomad4 AMR AF: 0.00111

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.000188

Gnomad4 NFE AF: 0.000955

Gnomad4 OTH AF: 0.000945

Alfa AF: 0.000822 Hom.: 0

Bravo AF: 0.000729

EpiCase AF: 0.000763

EpiControl AF: 0.000771

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jan 14, 2023

- -

DZIP1L-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

May 26, 2021

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	3.5
Dann	Benign	0.38

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: rs149714506; hg19: chr3-137781768;