19-1407781-A-T

Variant names:

• chr19-1407781-A-T
• rs1278085566
• NM_018959.4:c.8A>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018959.4(DAZAP1):​c.8A>T​(p.Asn3Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000176 in 1,077,984 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 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. N3S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000014 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000018 (0 hom.)
• Consequence: DAZAP1 NM_018959.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.142
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22427112).

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.8A>T	p.Asn3Ile	missense	Exon 1 of 12	NP_061832.2
	DAZAP1	NM_001352033.2		c.8A>T	p.Asn3Ile	missense	Exon 1 of 12	NP_001338962.1	K7EK33
	DAZAP1	NM_001352034.2		c.8A>T	p.Asn3Ile	missense	Exon 1 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.8A>T	p.Asn3Ile	missense	Exon 1 of 12	ENSP00000233078.4	Q96EP5-1
	DAZAP1	ENST00000875652.1		c.8A>T	p.Asn3Ile	missense	Exon 1 of 12	ENSP00000545711.1
	DAZAP1	ENST00000918388.1		c.8A>T	p.Asn3Ile	missense	Exon 1 of 12	ENSP00000588447.1

Frequencies

GnomAD3 genomes AF: 0.0000139 AC: 2 AN: 143596 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000308

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000182 AC: 17 AN: 934388 Hom.: 0 Cov.: 31 AF XY: 0.0000114 AC XY: 5 AN XY: 438704

African (AFR) AF: 0.00 AC: 0 AN: 17980

American (AMR) AF: 0.00 AC: 0 AN: 3826

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 8222

East Asian (EAS) AF: 0.00 AC: 0 AN: 13278

South Asian (SAS) AF: 0.00 AC: 0 AN: 18808

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10848

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2142

European-Non Finnish (NFE) AF: 0.0000194 AC: 16 AN: 826044

Other (OTH) AF: 0.0000301 AC: 1 AN: 33240

GnomAD4 genome AF: 0.0000139 AC: 2 AN: 143596 Hom.: 0 Cov.: 33 AF XY: 0.0000286 AC XY: 2 AN XY: 69948

African (AFR) AF: 0.00 AC: 0 AN: 39220

American (AMR) AF: 0.00 AC: 0 AN: 14680

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3336

East Asian (EAS) AF: 0.00 AC: 0 AN: 4790

South Asian (SAS) AF: 0.00 AC: 0 AN: 4652

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8810

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 278

European-Non Finnish (NFE) AF: 0.0000308 AC: 2 AN: 64986

Other (OTH) AF: 0.00 AC: 0 AN: 1984

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.053	T
Eigen	Benign	-0.13
Eigen_PC	Benign	-0.20
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.77	T
M_CAP	Pathogenic	0.56	D
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L
PhyloP100		-0.14
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-0.51	N
REVEL	Benign	0.12
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.036	D
Polyphen		0.99	D
Vest4		0.13
MutPred		0.23		Gain of catalytic residue at N3 (P = 0.064)
MVP		0.39
MPC		1.5
ClinPred		0.97	D
GERP RS		0.91
PromoterAI		0.028	Neutral
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		3.0
Varity_R		0.26
gMVP		0.60
Mutation Taster		=67/33	polymorphism

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: rs1278085566; hg19: chr19-1407780;