13-95586065-C-A

Position:

• chr13-95586065-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_198968.4(DZIP1):​c.2290G>T​(p.Val764Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: DZIP1 NM_198968.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0900

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12279868).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DZIP1	NM_198968.4	c.2290G>T	p.Val764Phe	missense_variant	21/23	ENST00000376829.7	NP_945319.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DZIP1	ENST00000376829.7	c.2290G>T	p.Val764Phe	missense_variant	21/23	1	NM_198968.4	ENSP00000366025.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

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

Jan 10, 2022

The c.2290G>T (p.V764F) alteration is located in exon 21 (coding exon 18) of the DZIP1 gene. This alteration results from a G to T substitution at nucleotide position 2290, causing the valine (V) at amino acid position 764 to be replaced by a phenylalanine (F). 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	Benign	0.085
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	11
DANN	Uncertain	0.99
DEOGEN2	Benign	0.29	.;T;.;T
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.46
FATHMM_MKL	Benign	0.39	N
LIST_S2	Benign	0.78	.;T;T;.
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.12	T;T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.7	.;L;.;L
PrimateAI	Benign	0.29	T
PROVEAN	Uncertain	-2.7	D;D;D;D
REVEL	Benign	0.088
Sift	Benign	0.043	D;D;D;D
Sift4G	Uncertain	0.0090	D;D;D;D
Polyphen		0.029	B;B;B;B
Vest4		0.21
MutPred		0.23		.;Gain of loop (P = 3e-04);.;Gain of loop (P = 3e-04);
MVP		0.54
MPC		0.10
ClinPred		0.38	T
GERP RS		2.8
Varity_R		0.089
gMVP		0.12

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: rs990381001; hg19: chr13-96238319;