rs767605428

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_198968.4(DZIP1):​c.2293G>C​(p.Gly765Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000412 in 1,457,920 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G765S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0000041 ( 0 hom. )

Consequence

DZIP1
NM_198968.4 missense

Scores

1
7
11

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.836
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 Likely_benign. Variant got -4 ACMG points.

BS2
High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DZIP1NM_198968.4 linkc.2293G>C p.Gly765Arg missense_variant Exon 21 of 23 ENST00000376829.7 NP_945319.1 Q86YF9-1B3KSP1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DZIP1ENST00000376829.7 linkc.2293G>C p.Gly765Arg missense_variant Exon 21 of 23 1 NM_198968.4 ENSP00000366025.2 Q86YF9-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000404
AC:
1
AN:
247444
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
133716
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:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000888
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000412
AC:
6
AN:
1457920
Hom.:
0
Cov.:
30
AF XY:
0.00000414
AC XY:
3
AN XY:
725064
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000540
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
EpiCase
AF:
0.0000549
EpiControl
AF:
0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.17
BayesDel_addAF
Benign
-0.12
T
BayesDel_noAF
Benign
-0.40
CADD
Benign
16
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.55
.;D;.;D
Eigen
Benign
-0.036
Eigen_PC
Benign
-0.16
FATHMM_MKL
Benign
0.58
D
LIST_S2
Uncertain
0.91
.;D;D;.
M_CAP
Benign
0.032
D
MetaRNN
Uncertain
0.68
D;D;D;D
MetaSVM
Benign
-0.95
T
MutationAssessor
Uncertain
2.1
.;M;.;M
PrimateAI
Benign
0.36
T
PROVEAN
Pathogenic
-4.9
D;D;D;D
REVEL
Benign
0.13
Sift
Uncertain
0.0040
D;D;D;D
Sift4G
Uncertain
0.0070
D;D;D;D
Polyphen
0.99
D;D;D;D
Vest4
0.72
MutPred
0.41
.;Gain of loop (P = 3e-04);.;Gain of loop (P = 3e-04);
MVP
0.58
MPC
0.10
ClinPred
0.86
D
GERP RS
2.8
Varity_R
0.20
gMVP
0.26

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: rs767605428; hg19: chr13-96238316; API