chr13-95590377-T-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_198968.4(DZIP1):​c.1745A>G​(p.His582Arg) 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. 14/21 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

Scores

16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.870
Variant links:
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]

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ACMG classification

Classification made for transcript

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=0.05944881).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
DZIP1NM_198968.4 linkuse as main transcriptc.1745A>G p.His582Arg missense_variant 17/23 ENST00000376829.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
DZIP1ENST00000376829.7 linkuse as main transcriptc.1745A>G p.His582Arg missense_variant 17/231 NM_198968.4 P2Q86YF9-1
DZIP1ENST00000361396.6 linkuse as main transcriptc.1688A>G p.His563Arg missense_variant 16/221 A2Q86YF9-2
DZIP1ENST00000347108.7 linkuse as main transcriptc.1745A>G p.His582Arg missense_variant 15/215 P2Q86YF9-1
DZIP1ENST00000361156.7 linkuse as main transcriptc.1688A>G p.His563Arg missense_variant 14/205 A2Q86YF9-2

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
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJul 19, 2023The c.1745A>G (p.H582R) alteration is located in exon 17 (coding exon 14) of the DZIP1 gene. This alteration results from a A to G substitution at nucleotide position 1745, causing the histidine (H) at amino acid position 582 to be replaced by an arginine (R). 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
0.059
BayesDel_addAF
Benign
-0.37
T
BayesDel_noAF
Benign
-0.77
CADD
Benign
4.0
DANN
Benign
0.27
Eigen
Benign
-0.88
Eigen_PC
Benign
-0.87
FATHMM_MKL
Benign
0.36
N
M_CAP
Benign
0.0054
T
MetaRNN
Benign
0.059
T;T;T;T
MetaSVM
Benign
-0.93
T
MutationTaster
Benign
1.0
N;N;N;N
PrimateAI
Benign
0.32
T
PROVEAN
Benign
-1.6
N;N;N;N
REVEL
Benign
0.038
Sift
Benign
0.49
T;T;T;T
Sift4G
Benign
0.10
T;T;T;T
Polyphen
0.037
B;B;B;B
Vest4
0.17
MutPred
0.17
.;Gain of MoRF binding (P = 0.0217);.;Gain of MoRF binding (P = 0.0217);
MVP
0.31
MPC
0.092
ClinPred
0.048
T
GERP RS
0.53
Varity_R
0.045
gMVP
0.069

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: chr13-96242631; API