chr13-95587722-G-A

Position:

• chr13-95587722-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_198968.4(DZIP1):​c.2035C>T​(p.Pro679Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DZIP1 NM_198968.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.06

Genes affected

DZIP1 (HGNC:20908): (DAZ interacting zinc finger protein 1) Predicted to enable metal ion binding activity. Involved in cilium assembly; germ cell development; and spermatogenesis. Located in cytosol; microtubule organizing center; and nucleoplasm. Colocalizes with centriole. Implicated in mitral valve prolapse and spermatogenic failure 47. [provided by Alliance of Genome Resources, Apr 2022]

DZIP1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DZIP1	NM_198968.4	c.2035C>T	p.Pro679Ser	missense_variant	20/23	ENST00000376829.7	NP_945319.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DZIP1	ENST00000376829.7	c.2035C>T	p.Pro679Ser	missense_variant	20/23	1	NM_198968.4	ENSP00000366025.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 10, 2024

The c.2035C>T (p.P679S) alteration is located in exon 20 (coding exon 17) of the DZIP1 gene. This alteration results from a C to T substitution at nucleotide position 2035, causing the proline (P) at amino acid position 679 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.67
BayesDel_addAF	Uncertain	0.023	T
BayesDel_noAF	Benign	-0.20
CADD	Uncertain	26
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.60	.;D;.;D
Eigen	Pathogenic	0.70
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.92	.;D;D;.
M_CAP	Benign	0.040	D
MetaRNN	Uncertain	0.71	D;D;D;D
MetaSVM	Benign	-0.64	T
MutationAssessor	Uncertain	2.6	.;M;.;M
PrimateAI	Benign	0.44	T
PROVEAN	Pathogenic	-6.0	D;D;D;D
REVEL	Benign	0.21
Sift	Pathogenic	0.0	D;D;D;D
Sift4G	Pathogenic	0.0	D;D;D;D
Polyphen		1.0	D;D;D;D
Vest4		0.64
MutPred		0.25		.;Gain of phosphorylation at P679 (P = 0.0196);.;Gain of phosphorylation at P679 (P = 0.0196);
MVP		0.70
MPC		0.43
ClinPred		0.99	D
GERP RS		5.3
Varity_R		0.69
gMVP		0.44

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.17		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr13-96239976;