rs1135402754

Positions:

• chr3-138103699-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2 PP3_Moderate PP5

The NM_173543.3(DZIP1L):​c.273G>C​(p.Gln91His) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,140 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: DZIP1L NM_173543.3 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 4.38

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.867
• PP5: Variant 3-138103699-C-G is Pathogenic according to our data. Variant chr3-138103699-C-G is described in ClinVar as [Pathogenic]. Clinvar id is 431432.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DZIP1L	NM_173543.3	c.273G>C	p.Gln91His	missense_variant	2/16	ENST00000327532.7	NP_775814.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DZIP1L	ENST00000327532.7	c.273G>C	p.Gln91His	missense_variant	2/16	1	NM_173543.3	ENSP00000332148.2
DZIP1L	ENST00000469243.5	c.273G>C	p.Gln91His	missense_variant	3/14	2		ENSP00000419486.1
DZIP1L	ENST00000490472.1	n.80G>C		non_coding_transcript_exon_variant	1/4	3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460140 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726452

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000756

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Polycystic kidney disease 5 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Aug 07, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.96
BayesDel_addAF	Pathogenic	0.31	D
BayesDel_noAF	Pathogenic	0.21
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.41	T;.
Eigen	Pathogenic	0.70
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.86	D;D
M_CAP	Uncertain	0.17	D
MetaRNN	Pathogenic	0.87	D;D
MetaSVM	Uncertain	0.16	D
MutationAssessor	Uncertain	2.8	M;M
PrimateAI	Uncertain	0.72	T
PROVEAN	Pathogenic	-4.7	D;D
REVEL	Pathogenic	0.71
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;D
Vest4		0.92
MutPred		0.62		Gain of methylation at R88 (P = 0.151);Gain of methylation at R88 (P = 0.151);
MVP		0.42
MPC		0.43
ClinPred		1.0	D
GERP RS		4.8
Varity_R		0.76
gMVP		0.77

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: rs1135402754; hg19: chr3-137822541;