19-1407781-A-C

Variant names:

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

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>C​(p.Asn3Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000214 in 934,386 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (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=0.15519881).

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>C	p.Asn3Thr	missense	Exon 1 of 12	NP_061832.2
	DAZAP1	NM_001352033.2		c.8A>C	p.Asn3Thr	missense	Exon 1 of 12	NP_001338962.1	K7EK33
	DAZAP1	NM_001352034.2		c.8A>C	p.Asn3Thr	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>C	p.Asn3Thr	missense	Exon 1 of 12	ENSP00000233078.4	Q96EP5-1
	DAZAP1	ENST00000875652.1		c.8A>C	p.Asn3Thr	missense	Exon 1 of 12	ENSP00000545711.1
	DAZAP1	ENST00000918388.1		c.8A>C	p.Asn3Thr	missense	Exon 1 of 12	ENSP00000588447.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000214 AC: 2 AN: 934386 Hom.: 0 Cov.: 31 AF XY: 0.00000228 AC XY: 1 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: 0.00000242 AC: 2 AN: 826042

Other (OTH) AF: 0.00 AC: 0 AN: 33240

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	22
DANN	Benign	0.94
DEOGEN2	Benign	0.039	T
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.30
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.64	T
M_CAP	Pathogenic	0.41	D
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.79	N
PhyloP100		-0.14
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-0.23	N
REVEL	Benign	0.088
Sift	Uncertain	0.0050	D
Sift4G	Benign	0.12	T
Polyphen		0.89	P
Vest4		0.13
MutPred		0.17		Gain of glycosylation at N3 (P = 0.0341)
MVP		0.41
MPC		1.3
ClinPred		0.23	T
GERP RS		0.91
PromoterAI		-0.057	Neutral
Varity_R		0.10
gMVP		0.35
Mutation Taster		=66/34	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;