19-1423200-A-G

Variant names:

• chr19-1423200-A-G
• rs4807927
• NM_018959.4:c.463+804A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018959.4(DAZAP1):​c.463+804A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.277 in 152,180 control chromosomes in the GnomAD database, including 10,365 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.28 (10365 hom., cov: 33)
• Consequence: DAZAP1 NM_018959.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.55
• Publications: 10 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.635 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018959.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DAZAP1	NM_018959.4	MANE Select	c.463+804A>G		intron	N/A	NP_061832.2
	DAZAP1	NM_001352033.2		c.460+804A>G		intron	N/A	NP_001338962.1
	DAZAP1	NM_001352034.2		c.463+804A>G		intron	N/A	NP_001338963.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DAZAP1	ENST00000233078.9	TSL:1 MANE Select	c.463+804A>G		intron	N/A	ENSP00000233078.4
	DAZAP1	ENST00000587079.5	TSL:5	c.460+804A>G		intron	N/A	ENSP00000465433.2
	DAZAP1	ENST00000592522.5	TSL:5	c.463+804A>G		intron	N/A	ENSP00000467680.2

Frequencies

GnomAD3 genomes AF: 0.276 AC: 42032 AN: 152064 Hom.: 10308 Cov.: 33

Gnomad AFR AF: 0.641

Gnomad AMI AF: 0.0515

Gnomad AMR AF: 0.321

Gnomad ASJ AF: 0.103

Gnomad EAS AF: 0.360

Gnomad SAS AF: 0.259

Gnomad FIN AF: 0.0845

Gnomad MID AF: 0.118

Gnomad NFE AF: 0.0826

Gnomad OTH AF: 0.257

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.277 AC: 42161 AN: 152180 Hom.: 10365 Cov.: 33 AF XY: 0.281 AC XY: 20898 AN XY: 74420

African (AFR) AF: 0.641 AC: 26613 AN: 41512

American (AMR) AF: 0.323 AC: 4932 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.103 AC: 356 AN: 3466

East Asian (EAS) AF: 0.360 AC: 1860 AN: 5168

South Asian (SAS) AF: 0.258 AC: 1246 AN: 4828

European-Finnish (FIN) AF: 0.0845 AC: 896 AN: 10606

Middle Eastern (MID) AF: 0.123 AC: 36 AN: 292

European-Non Finnish (NFE) AF: 0.0826 AC: 5614 AN: 67996

Other (OTH) AF: 0.265 AC: 561 AN: 2114

Alfa AF: 0.190 Hom.: 1575

Bravo AF: 0.306

Asia WGS AF: 0.391 AC: 1358 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	18
DANN	Benign	0.53
PhyloP100		1.6
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4807927; hg19: chr19-1423199;