rs1220814973

Variant names:

• chr12-4626614-TTG-T
• rs1220814973
• NM_001278309.2:c.2286_2287delCA

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP5

The NM_001278309.2(AKAP3):​c.2286_2287delCA​(p.His762GlnfsTer22) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 33)
• Consequence: AKAP3 NM_001278309.2 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 4.43
• Publications: 1 publications found

Genes affected

AKAP3 (HGNC:373): (A-kinase anchoring protein 3) This gene encodes a member of A-kinase anchoring proteins (AKAPs), a family of functionally related proteins that target protein kinase A to discrete locations within the cell. The encoded protein is reported to participate in protein-protein interactions with the R-subunit of the protein kinase A as well as sperm-associated proteins. This protein is expressed in spermatozoa and localized to the acrosomal region of the sperm head as well as the length of the principal piece. It may function as a regulator of motility, capacitation, and the acrosome reaction. [provided by RefSeq, May 2013]

AKAP3 Gene-Disease associations (from GenCC):

• spermatogenic failure 82

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ENSG00000272921 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 12-4626614-TTG-T is Pathogenic according to our data. Variant chr12-4626614-TTG-T is described in ClinVar as Pathogenic. ClinVar VariationId is 2500165.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001278309.2. 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
	AKAP3	NM_001278309.2	MANE Select	c.2286_2287delCA	p.His762GlnfsTer22	frameshift	Exon 5 of 6	NP_001265238.2	O75969
	AKAP3	NM_006422.4		c.2286_2287delCA	p.His762GlnfsTer22	frameshift	Exon 5 of 6	NP_006413.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AKAP3	ENST00000228850.6	TSL:5 MANE Select	c.2286_2287delCA	p.His762GlnfsTer22	frameshift	Exon 5 of 6	ENSP00000228850.1	O75969
	ENSG00000272921	ENST00000536588.1	TSL:3	n.142-4705_142-4704delTG		intron	N/A	ENSP00000445121.1	H0YGX0
	AKAP3	ENST00000545990.6	TSL:2	c.2286_2287delCA	p.His762GlnfsTer22	frameshift	Exon 5 of 6	ENSP00000440994.1	O75969

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions as Germline

Significance: Pathogenic

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
1	-	-	Spermatogenic failure 82 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.4
Mutation Taster		=44/156	disease causing (fs/PTC)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1220814973; hg19: chr12-4735780;