NM_198968.4:c.1990A>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_198968.4(DZIP1):c.1990A>T(p.Met664Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00377 in 1,606,368 control chromosomes in the GnomAD database, including 151 homozygotes. 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 Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M664V) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.018 ( 78 hom., cov: 33)

Exomes 𝑓: 0.0023 ( 73 hom. )

Consequence

DZIP1
NM_198968.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.22

Publications

4 publications found

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]

DZIP1 Gene-Disease associations (from GenCC):

spermatogenic failure 47
Inheritance: AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

DZIP1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0023871958).

BP6

Variant 13-95589191-T-A is Benign according to our data. Variant chr13-95589191-T-A is described in ClinVar as Benign. ClinVar VariationId is 776804.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0598 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198968.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DZIP1	NM_198968.4	MANE Select	c.1990A>T	p.Met664Leu	missense	Exon 19 of 23	NP_945319.1	Q86YF9-1
	DZIP1	NM_014934.5		c.1933A>T	p.Met645Leu	missense	Exon 18 of 22	NP_055749.1	Q86YF9-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DZIP1	ENST00000376829.7	TSL:1 MANE Select	c.1990A>T	p.Met664Leu	missense	Exon 19 of 23	ENSP00000366025.2	Q86YF9-1
DZIP1	ENST00000361396.6	TSL:1	c.1933A>T	p.Met645Leu	missense	Exon 18 of 22	ENSP00000355175.2	Q86YF9-2
DZIP1	ENST00000926439.1		c.2044A>T	p.Met682Leu	missense	Exon 16 of 20	ENSP00000596498.1

Frequencies

GnomAD3 genomes

AF:

0.0180

AC:

2740

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0616

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00681

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000676

Gnomad OTH

AF:

0.0129

GnomAD2 exomes

AF:

0.00470

AC:

1156

AN:

245950

AF XY:

0.00325

show subpopulations

Gnomad AFR exome

AF:

0.0605

Gnomad AMR exome

AF:

0.00350

Gnomad ASJ exome

AF:

0.000402

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000453

Gnomad OTH exome

AF:

0.00200

GnomAD4 exome

AF:

0.00227

AC:

3302

AN:

1454058

Hom.:

Cov.:

AF XY:

0.00203

AC XY:

1471

AN XY:

723054

show subpopulations

African (AFR)

AF:

0.0653

AC:

2152

AN:

32958

American (AMR)

AF:

0.00402

AC:

175

AN:

43526

Ashkenazi Jewish (ASJ)

AF:

0.000538

AC:

AN:

26028

East Asian (EAS)

AF:

0.00

AC:

AN:

39532

South Asian (SAS)

AF:

0.000262

AC:

AN:

84064

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53368

Middle Eastern (MID)

AF:

0.00384

AC:

AN:

5724

European-Non Finnish (NFE)

AF:

0.000543

AC:

602

AN:

1108732

Other (OTH)

AF:

0.00524

AC:

315

AN:

60126

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.452

Heterozygous variant carriers

140

280

421

561

701

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

156

234

312

390

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0181

AC:

2754

AN:

152310

Hom.:

Cov.:

AF XY:

0.0174

AC XY:

1297

AN XY:

74488

show subpopulations

African (AFR)

AF:

0.0618

AC:

2568

AN:

41558

American (AMR)

AF:

0.00680

AC:

104

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00104

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000676

AC:

AN:

68026

Other (OTH)

AF:

0.0128

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

130

260

389

519

649

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

160

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00136

Hom.:

Bravo

AF:

0.0207

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.0586

AC:

258

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00574

AC:

697

Asia WGS

AF:

0.00722

AC:

AN:

3478

EpiCase

AF:

0.000878

EpiControl

AF:

0.000892

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.76

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.069

(source)

DANN

Benign

0.44

DEOGEN2

Benign

0.017

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.023

LIST_S2

Benign

0.55

MetaRNN

Benign

0.0024

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

PhyloP100

-1.2

PrimateAI

Benign

0.23

PROVEAN

Benign

-0.090

REVEL

Benign

0.0090

Sift

Benign

0.46

Sift4G

Benign

0.80

Polyphen

0.0

Vest4

0.091

MutPred

0.26

Gain of catalytic residue at M664 (P = 0.002)

MVP

0.24

MPC

0.071

ClinPred

0.0016

GERP RS

-6.8

Varity_R

0.045

gMVP

0.070

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over