NM_018959.4:c.813T>C

Variant names:

• chr19-1430304-T-C
• rs113778676
• NM_018959.4:c.813T>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_018959.4(DAZAP1):​c.813T>C​(p.Pro271Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0024 in 1,297,966 control chromosomes in the GnomAD database, including 68 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.012 (35 hom., cov: 32)
  • Exomes 𝑓: 0.0013 (33 hom.)
• Consequence: DAZAP1 NM_018959.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -6.92
• 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: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 19-1430304-T-C is Benign according to our data. Variant chr19-1430304-T-C is described in ClinVar as Benign. ClinVar VariationId is 768947.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-6.93 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0123 (1644/133462) while in subpopulation AFR AF = 0.0425 (1576/37110). AF 95% confidence interval is 0.0407. There are 35 homozygotes in GnomAd4. There are 750 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 35 gene

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.813T>C	p.Pro271Pro	synonymous	Exon 10 of 12	NP_061832.2
	DAZAP1	NM_001352033.2		c.810T>C	p.Pro270Pro	synonymous	Exon 10 of 12	NP_001338962.1	K7EK33
	DAZAP1	NM_001352034.2		c.813T>C	p.Pro271Pro	synonymous	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.813T>C	p.Pro271Pro	synonymous	Exon 10 of 12	ENSP00000233078.4	Q96EP5-1
	DAZAP1	ENST00000875652.1		c.1002T>C	p.Pro334Pro	synonymous	Exon 10 of 12	ENSP00000545711.1
	DAZAP1	ENST00000918388.1		c.999T>C	p.Pro333Pro	synonymous	Exon 10 of 12	ENSP00000588447.1

Frequencies

GnomAD3 genomes AF: 0.0123 AC: 1635 AN: 133352 Hom.: 34 Cov.: 32

Gnomad AFR AF: 0.0423

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00279

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: 0.0000663

Gnomad OTH AF: 0.0127

GnomAD2 exomes AF: 0.00299 AC: 604 AN: 202192 AF XY: 0.00215

Gnomad AFR exome AF: 0.0385

Gnomad AMR exome AF: 0.00102

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000612

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000219

Gnomad OTH exome AF: 0.000624

GnomAD4 exome AF: 0.00126 AC: 1466 AN: 1164504 Hom.: 33 Cov.: 31 AF XY: 0.00112 AC XY: 648 AN XY: 576154

African (AFR) AF: 0.0479 AC: 1239 AN: 25868

American (AMR) AF: 0.00159 AC: 51 AN: 32136

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15000

East Asian (EAS) AF: 0.0000458 AC: 1 AN: 21822

South Asian (SAS) AF: 0.0000689 AC: 5 AN: 72594

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33084

Middle Eastern (MID) AF: 0.000946 AC: 4 AN: 4230

European-Non Finnish (NFE) AF: 0.0000207 AC: 19 AN: 916014

Other (OTH) AF: 0.00336 AC: 147 AN: 43756

GnomAD4 genome AF: 0.0123 AC: 1644 AN: 133462 Hom.: 35 Cov.: 32 AF XY: 0.0115 AC XY: 750 AN XY: 65286

African (AFR) AF: 0.0425 AC: 1576 AN: 37110

American (AMR) AF: 0.00279 AC: 39 AN: 14002

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3166

East Asian (EAS) AF: 0.00 AC: 0 AN: 3984

South Asian (SAS) AF: 0.00 AC: 0 AN: 3628

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8332

Middle Eastern (MID) AF: 0.00362 AC: 1 AN: 276

European-Non Finnish (NFE) AF: 0.0000663 AC: 4 AN: 60290

Other (OTH) AF: 0.0126 AC: 24 AN: 1908

Alfa AF: 0.0112 Hom.: 7

Bravo AF: 0.0120

Asia WGS AF: 0.00606 AC: 21 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.13
DANN	Benign	0.33
PhyloP100		-6.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	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: rs113778676; hg19: chr19-1430303; COSMIC: COSV51836433; COSMIC: COSV51836433;