Variant chr19-1407781-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_018959.4(DAZAP1):c.8A>G(p.Asn3Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000464 in 1,077,984 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000014 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000032 ( 0 hom. )

Consequence

DAZAP1
NM_018959.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.142

Variant links:

Genes affected

DAZAP1 (HGNC:2683): (DAZ associated protein 1) In mammals, the Y chromosome directs the development of the testes and plays an important role in spermatogenesis. A high percentage of infertile men have deletions that map to regions of the Y chromosome. The DAZ (deleted in azoospermia) gene cluster maps to the AZFc region of the Y chromosome and is deleted in many azoospermic and severely oligospermic men. It is thought that the DAZ gene cluster arose from the transposition, amplification, and pruning of the ancestral autosomal gene DAZL also involved in germ cell development and gametogenesis. This gene encodes a RNA-binding protein with two RNP motifs that was originally identified by its interaction with the infertility factors DAZ and DAZL. Two isoforms are encoded by transcript variants of this gene. [provided by RefSeq, Jul 2008]

DAZAP1 links:

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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=0.09374204).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DAZAP1	NM_018959.4 linkuse as main transcript	c.8A>G	p.Asn3Ser	missense_variant	1/12	ENST00000233078.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DAZAP1	ENST00000233078.9 linkuse as main transcript	c.8A>G	p.Asn3Ser	missense_variant	1/12	1	NM_018959.4	P4	Q96EP5-1

Frequencies

GnomAD3 genomes

AF:

0.0000139

AC:

AN:

143596

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000418

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000321

AC:

AN:

934388

Hom.:

Cov.:

AF XY:

0.00000684

AC XY:

AN XY:

438704

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000753

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000121

Gnomad4 OTH exome

AF:

0.0000301

GnomAD4 genome

AF:

0.0000139

AC:

AN:

143596

Hom.:

Cov.:

AF XY:

0.0000286

AC XY:

AN XY:

69948

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000418

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

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 submitter

clinical testing

Ambry Genetics

Jan 30, 2024

The c.8A>G (p.N3S) alteration is located in exon 1 (coding exon 1) of the DAZAP1 gene. This alteration results from a A to G substitution at nucleotide position 8, causing the asparagine (N) at amino acid position 3 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

0.055

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.72

CADD

Benign

DANN

Benign

0.93

Eigen

Benign

-0.44

Eigen_PC

Benign

-0.43

FATHMM_MKL

Benign

0.032

LIST_S2

Benign

0.73

T;T;T;T;T

M_CAP

Pathogenic

0.39

MetaRNN

Benign

0.094

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.2

N;N;.;.;.

MutationTaster

Benign

0.53

N;N

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

0.060

N;N;.;.;.

REVEL

Benign

0.15

Sift

Benign

0.26

T;T;.;.;.

Sift4G

Benign

0.23

T;T;T;T;T

Polyphen

0.89

P;P;.;.;.

Vest4

0.095

MutPred

0.17

Gain of phosphorylation at N3 (P = 0.0767);Gain of phosphorylation at N3 (P = 0.0767);Gain of phosphorylation at N3 (P = 0.0767);Gain of phosphorylation at N3 (P = 0.0767);Gain of phosphorylation at N3 (P = 0.0767);

MVP

0.45

MPC

1.0

ClinPred

0.58

GERP RS

0.91

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

3.0

Varity_R

0.036

gMVP

0.28

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over