chr13-95589176-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_198968.4(DZIP1):​c.2005C>T​(p.Pro669Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,454,126 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

DZIP1
NM_198968.4 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.67
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.11008212).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
DZIP1NM_198968.4 linkuse as main transcriptc.2005C>T p.Pro669Ser missense_variant 19/23 ENST00000376829.7 NP_945319.1 Q86YF9-1B3KSP1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
DZIP1ENST00000376829.7 linkuse as main transcriptc.2005C>T p.Pro669Ser missense_variant 19/231 NM_198968.4 ENSP00000366025.2 Q86YF9-1
DZIP1ENST00000361396.6 linkuse as main transcriptc.1948C>T p.Pro650Ser missense_variant 18/221 ENSP00000355175.2 Q86YF9-2
DZIP1ENST00000347108.7 linkuse as main transcriptc.2005C>T p.Pro669Ser missense_variant 17/215 ENSP00000257312.5 Q86YF9-1
DZIP1ENST00000361156.7 linkuse as main transcriptc.1948C>T p.Pro650Ser missense_variant 16/205 ENSP00000355018.3 Q86YF9-2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000409
AC:
1
AN:
244352
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
131900
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000354
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000206
AC:
3
AN:
1454126
Hom.:
0
Cov.:
29
AF XY:
0.00000277
AC XY:
2
AN XY:
722932
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000358
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
ExAC
AF:
0.00000824
AC:
1

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 GeneticsOct 02, 2023The c.2005C>T (p.P669S) alteration is located in exon 19 (coding exon 16) of the DZIP1 gene. This alteration results from a C to T substitution at nucleotide position 2005, causing the proline (P) at amino acid position 669 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
Benign
0.086
BayesDel_addAF
Benign
-0.33
T
BayesDel_noAF
Benign
-0.60
CADD
Benign
16
DANN
Benign
0.97
DEOGEN2
Benign
0.044
.;T;.;T
Eigen
Benign
-0.17
Eigen_PC
Benign
-0.0066
FATHMM_MKL
Uncertain
0.85
D
LIST_S2
Benign
0.71
.;T;T;.
M_CAP
Benign
0.0046
T
MetaRNN
Benign
0.11
T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.4
.;L;.;L
PrimateAI
Benign
0.31
T
PROVEAN
Benign
-2.1
N;N;N;N
REVEL
Benign
0.043
Sift
Benign
0.31
T;T;T;T
Sift4G
Benign
0.43
T;T;T;T
Polyphen
0.037
B;B;B;B
Vest4
0.20
MutPred
0.24
.;Gain of loop (P = 0.0013);.;Gain of loop (P = 0.0013);
MVP
0.52
MPC
0.11
ClinPred
0.18
T
GERP RS
4.8
Varity_R
0.066
gMVP
0.093

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs761770434; hg19: chr13-96241430; COSMIC: COSV61271752; COSMIC: COSV61271752; API