3-138062836-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_173543.3(DZIP1L):c.2284C>T(p.Pro762Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000649 in 1,614,080 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00060 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00065 (5 hom.)
• Consequence: DZIP1L NM_173543.3 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.225

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.003020227).
• BP6: Variant 3-138062836-G-A is Benign according to our data. Variant chr3-138062836-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 722788.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000597 (91/152342) while in subpopulation SAS AF= 0.00497 (24/4826). AF 95% confidence interval is 0.00343. There are 1 homozygotes in gnomad4. There are 49 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DZIP1L	NM_173543.3	c.2284C>T	p.Pro762Ser	missense_variant	16/16	ENST00000327532.7
DZIP1L	XM_005247198.4	c.2368C>T	p.Pro790Ser	missense_variant	16/16
DZIP1L	XM_047447642.1	c.2227C>T	p.Pro743Ser	missense_variant	15/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DZIP1L	ENST00000327532.7	c.2284C>T	p.Pro762Ser	missense_variant	16/16	1	NM_173543.3	P2

Frequencies

GnomAD3 genomes AF: 0.000598 AC: 91 AN: 152224 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.0000482

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.000720

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00497

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000544

Gnomad OTH AF: 0.000957

GnomAD3 exomes AF: 0.000939 AC: 236 AN: 251382 Hom.: 2 AF XY: 0.00122 AC XY: 166 AN XY: 135856

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.000405

Gnomad ASJ exome AF: 0.000794

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.00399

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.000739

Gnomad OTH exome AF: 0.000652

GnomAD4 exome AF: 0.000654 AC: 956 AN: 1461738 Hom.: 5 Cov.: 31 AF XY: 0.000813 AC XY: 591 AN XY: 727176

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000470

Gnomad4 ASJ exome AF: 0.000995

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00453

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.000380

Gnomad4 OTH exome AF: 0.00114

GnomAD4 genome AF: 0.000597 AC: 91 AN: 152342 Hom.: 1 Cov.: 32 AF XY: 0.000658 AC XY: 49 AN XY: 74500

Gnomad4 AFR AF: 0.0000481

Gnomad4 AMR AF: 0.000719

Gnomad4 ASJ AF: 0.000576

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00497

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000544

Gnomad4 OTH AF: 0.000947

Alfa AF: 0.000594 Hom.: 1

Bravo AF: 0.000518

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.000581 AC: 5

ExAC AF: 0.000947 AC: 115

Asia WGS AF: 0.00173 AC: 6 AN: 3478

EpiCase AF: 0.00104

EpiControl AF: 0.00148

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Nov 27, 2023

- -

DZIP1L-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 26, 2020

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
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.68	T
BayesDel_noAF	Benign	-0.75
Cadd	Benign	6.2
Dann	Benign	0.51
DEOGEN2	Benign	0.012	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.083	N
LIST_S2	Benign	0.51	T
M_CAP	Benign	0.0028	T
MetaRNN	Benign	0.0030	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.47	N
REVEL	Benign	0.017
Sift	Benign	0.18	T
Sift4G	Benign	0.30	T
Polyphen		0.093	B
Vest4		0.11
MVP		0.030
MPC		0.090
ClinPred		0.0040	T
GERP RS		0.0090
Varity_R		0.022
gMVP		0.28

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: rs142617141; hg19: chr3-137781678;