chr12-51242348-C-T

Variant names:

• chr12-51242348-C-T
• rs1247980992
• NM_014764.4:c.397C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_014764.4(DAZAP2):​c.397C>T​(p.Pro133Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000118 in 1,445,692 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P133L) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: DAZAP2 NM_014764.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.28
• Publications: 0 publications found

Genes affected

DAZAP2 (HGNC:2684): (DAZ associated protein 2) This gene encodes a proline-rich protein which interacts with the deleted in azoospermia (DAZ) and the deleted in azoospermia-like gene through the DAZ-like repeats. This protein also interacts with the transforming growth factor-beta signaling molecule SARA (Smad anchor for receptor activation), eukaryotic initiation factor 4G, and an E3 ubiquitinase that regulates its stability in splicing factor containing nuclear speckles. The encoded protein may function in various biological and pathological processes including spermatogenesis, cell signaling and transcription regulation, formation of stress granules during translation arrest, RNA splicing, and pathogenesis of multiple myeloma. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.370018).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014764.4. 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
	DAZAP2	NM_014764.4	MANE Select	c.397C>T	p.Pro133Ser	missense	Exon 4 of 4	NP_055579.1	Q15038-1
	DAZAP2	NM_001136266.2		c.320C>T	p.Pro107Leu	missense	Exon 4 of 4	NP_001129738.1	Q15038-5
	DAZAP2	NM_001136264.2		c.331C>T	p.Pro111Ser	missense	Exon 5 of 5	NP_001129736.1	Q15038-6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DAZAP2	ENST00000412716.8	TSL:1 MANE Select	c.397C>T	p.Pro133Ser	missense	Exon 4 of 4	ENSP00000394699.2	Q15038-1
	DAZAP2	ENST00000549555.5	TSL:2	c.320C>T	p.Pro107Leu	missense	Exon 4 of 4	ENSP00000448051.1	Q15038-5
	DAZAP2	ENST00000449723.7	TSL:5	c.331C>T	p.Pro111Ser	missense	Exon 5 of 5	ENSP00000412812.2	Q15038-6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000125 AC: 3 AN: 239202 AF XY: 0.0000154

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000318

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000111

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000118 AC: 17 AN: 1445692 Hom.: 0 Cov.: 30 AF XY: 0.0000167 AC XY: 12 AN XY: 717960

African (AFR) AF: 0.00 AC: 0 AN: 32888

American (AMR) AF: 0.0000239 AC: 1 AN: 41778

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25086

East Asian (EAS) AF: 0.0000760 AC: 3 AN: 39498

South Asian (SAS) AF: 0.00 AC: 0 AN: 84358

European-Finnish (FIN) AF: 0.0000377 AC: 2 AN: 52990

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5690

European-Non Finnish (NFE) AF: 0.00000997 AC: 11 AN: 1103762

Other (OTH) AF: 0.00 AC: 0 AN: 59642

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.61
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.40
CADD	Uncertain	25
DANN	Uncertain	1.0
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.56	T
M_CAP	Benign	0.070	D
MetaRNN	Benign	0.37	T
MetaSVM	Benign	-0.96	T
PhyloP100		5.3
PrimateAI	Benign	0.40	T
PROVEAN	Pathogenic	-4.9	D
REVEL	Benign	0.16
Sift	Uncertain	0.0040	D
Vest4		0.45
MutPred		0.41		Loss of loop (P = 0.0022)
MVP		0.26
MPC		0.50
ClinPred		0.87	D
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.13
gMVP		0.26
Mutation Taster		=62/38	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: rs1247980992; hg19: chr12-51636132;