19-1430317-C-T

Variant names:

• chr19-1430317-C-T
• rs1317228854
• NM_018959.4:c.826C>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.826C>T​(p.Pro276Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000657 in 152,108 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. P276A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DAZAP1 NM_018959.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.90
• 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=0.23460567).

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.826C>T	p.Pro276Ser	missense	Exon 10 of 12	NP_061832.2
	DAZAP1	NM_001352033.2		c.823C>T	p.Pro275Ser	missense	Exon 10 of 12	NP_001338962.1	K7EK33
	DAZAP1	NM_001352034.2		c.826C>T	p.Pro276Ser	missense	Exon 10 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.826C>T	p.Pro276Ser	missense	Exon 10 of 12	ENSP00000233078.4	Q96EP5-1
	DAZAP1	ENST00000875652.1		c.1015C>T	p.Pro339Ser	missense	Exon 10 of 12	ENSP00000545711.1
	DAZAP1	ENST00000918388.1		c.1012C>T	p.Pro338Ser	missense	Exon 10 of 12	ENSP00000588447.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152108 Hom.: 0 Cov.: 32

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1416118 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 701484

African (AFR) AF: 0.00 AC: 0 AN: 31950

American (AMR) AF: 0.00 AC: 0 AN: 37972

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22560

East Asian (EAS) AF: 0.00 AC: 0 AN: 39078

South Asian (SAS) AF: 0.00 AC: 0 AN: 78040

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50788

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5442

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1091804

Other (OTH) AF: 0.00 AC: 0 AN: 58484

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152108 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74314

African (AFR) AF: 0.00 AC: 0 AN: 41412

American (AMR) AF: 0.00 AC: 0 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10632

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67968

Other (OTH) AF: 0.00 AC: 0 AN: 2090

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	Benign	0.073
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.42
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	T
Eigen	Benign	0.0077
Eigen_PC	Benign	0.13
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		5.9
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.060
Sift	Benign	0.031	D
Sift4G	Benign	0.46	T
Polyphen		0.57	P
Vest4		0.49
MutPred		0.24		Gain of phosphorylation at P276 (P = 0.0269)
MVP		0.36
MPC		0.81
ClinPred		0.86	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.15
gMVP		0.51
Mutation Taster		=72/28	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: rs1317228854; hg19: chr19-1430316; COSMIC: COSV51836308; COSMIC: COSV51836308;