chr19-1418703-C-G

Variant names:

• chr19-1418703-C-G
• rs2067862763
• NM_018959.4:c.275C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_018959.4(DAZAP1):​c.275C>G​(p.Pro92Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. P92L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DAZAP1 NM_018959.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.67
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DAZAP1	NM_018959.4	MANE Select	c.275C>G	p.Pro92Arg	missense	Exon 4 of 12	NP_061832.2
	DAZAP1	NM_001352033.2		c.275C>G	p.Pro92Arg	missense	Exon 4 of 12	NP_001338962.1	K7EK33
	DAZAP1	NM_001352034.2		c.275C>G	p.Pro92Arg	missense	Exon 4 of 12	NP_001338963.1	K7EQ55

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DAZAP1	ENST00000233078.9	TSL:1 MANE Select	c.275C>G	p.Pro92Arg	missense	Exon 4 of 12	ENSP00000233078.4	Q96EP5-1
	DAZAP1	ENST00000875652.1		c.275C>G	p.Pro92Arg	missense	Exon 4 of 12	ENSP00000545711.1
	DAZAP1	ENST00000918388.1		c.275C>G	p.Pro92Arg	missense	Exon 4 of 12	ENSP00000588447.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.61
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.061	T
Eigen	Uncertain	0.19
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.063	D
MetaRNN	Uncertain	0.48	T
MetaSVM	Benign	-0.42	T
MutationAssessor	Benign	0.94	L
PhyloP100		7.7
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-0.91	N
REVEL	Uncertain	0.36
Sift	Benign	0.042	D
Sift4G	Benign	0.26	T
Polyphen		0.24	B
Vest4		0.60
MutPred		0.29		Gain of MoRF binding (P = 7e-04)
MVP		0.80
MPC		1.3
ClinPred		0.86	D
GERP RS		4.8
Varity_R		0.19
gMVP		0.75
Mutation Taster		=38/62	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs2067862763; hg19: chr19-1418702;