3-138062926-G-A

Variant names:

• chr3-138062926-G-A
• rs149714506
• NM_173543.3:c.2194C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS1

The NM_173543.3(DZIP1L):​c.2194C>T​(p.Leu732Leu) 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, single submitter B:2
• Conservation: PhyloP100: 1.42
• 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 -11 ACMG points.

• 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 VariationId is 1462795.Status of the report is criteria_provided_single_submitter, 1 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

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.2194C>T	p.Leu732Leu	synonymous	Exon 16 of 16	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.2194C>T	p.Leu732Leu	synonymous	Exon 16 of 16	ENSP00000332148.2	Q8IYY4-1
	DZIP1L	ENST00000851674.1		c.2194C>T	p.Leu732Leu	synonymous	Exon 16 of 16	ENSP00000521733.1
	DZIP1L	ENST00000912002.1		c.2194C>T	p.Leu732Leu	synonymous	Exon 16 of 16	ENSP00000582061.1

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

GnomAD2 exomes AF: 0.000589 AC: 148 AN: 251454 AF XY: 0.000567

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 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

African (AFR) AF: 0.000149 AC: 5 AN: 33480

American (AMR) AF: 0.000358 AC: 16 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000661 AC: 57 AN: 86256

European-Finnish (FIN) AF: 0.000150 AC: 8 AN: 53408

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5768

European-Non Finnish (NFE) AF: 0.00112 AC: 1249 AN: 1112010

Other (OTH) AF: 0.000811 AC: 49 AN: 60392

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

African (AFR) AF: 0.000144 AC: 6 AN: 41566

American (AMR) AF: 0.00111 AC: 17 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.000188 AC: 2 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000955 AC: 65 AN: 68028

Other (OTH) AF: 0.000945 AC: 2 AN: 2116

Alfa AF: 0.000822 Hom.: 0

Bravo AF: 0.000729

EpiCase AF: 0.000763

EpiControl AF: 0.000771

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	DZIP1L-related disorder (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.5
DANN	Benign	0.38
PhyloP100		1.4
Mutation Taster		=100/0	polymorphism

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: rs149714506; hg19: chr3-137781768; COSMIC: COSV108170228; COSMIC: COSV108170228;