13-95589907-A-C

Position:

• chr13-95589907-A-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_198968.4(DZIP1):​c.1869T>G​(p.Asp623Glu) 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. 15/21 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: -1.39

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.030394882).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DZIP1	NM_198968.4	c.1869T>G	p.Asp623Glu	missense_variant	18/23	ENST00000376829.7	NP_945319.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DZIP1	ENST00000376829.7	c.1869T>G	p.Asp623Glu	missense_variant	18/23	1	NM_198968.4	ENSP00000366025.2
DZIP1	ENST00000361396.6	c.1812T>G	p.Asp604Glu	missense_variant	17/22	1		ENSP00000355175.2
DZIP1	ENST00000347108.7	c.1869T>G	p.Asp623Glu	missense_variant	16/21	5		ENSP00000257312.5
DZIP1	ENST00000361156.7	c.1812T>G	p.Asp604Glu	missense_variant	15/20	5		ENSP00000355018.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

Jan 09, 2024

The c.1869T>G (p.D623E) alteration is located in exon 18 (coding exon 15) of the DZIP1 gene. This alteration results from a T to G substitution at nucleotide position 1869, causing the aspartic acid (D) at amino acid position 623 to be replaced by a glutamic acid (E). 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	0.11
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.19
DANN	Benign	0.53
DEOGEN2	Benign	0.020	.;T;.;T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.018	N
LIST_S2	Benign	0.62	.;T;T;.
M_CAP	Benign	0.0020	T
MetaRNN	Benign	0.030	T;T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.64	.;N;.;N
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.31	N;N;N;N
REVEL	Benign	0.058
Sift	Benign	0.87	T;T;T;T
Sift4G	Benign	1.0	T;T;T;T
Polyphen		0.0010	B;B;B;B
Vest4		0.028
MutPred		0.12		.;Gain of catalytic residue at D623 (P = 0.1571);.;Gain of catalytic residue at D623 (P = 0.1571);
MVP		0.19
MPC		0.072
ClinPred		0.019	T
GERP RS		-11
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.028
gMVP		0.066

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr13-96242161;