AKAP3 p.Val824Val

Variant names:

• chr12-4615828-G-G
• NM_001278309.2:c.

Your query was ambiguous. Multiple possible variants found:

• chr12-4615829--
• chr12-4615829-C-A
• chr12-4615829-C-G
• chr12-4615829-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001278309.2(AKAP3):​c. variant causes a exon region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: AKAP3 NM_001278309.2 exon_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.647
• Publications: 0 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.		exon_region	Exon 6 of 6	NP_001265238.2	O75969
	AKAP3	NM_006422.4		c.		exon_region	Exon 6 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.		exon_region	Exon 6 of 6	ENSP00000228850.1	O75969
	ENSG00000272921	ENST00000536588.1	TSL:3	n.		intron	N/A	ENSP00000445121.1	H0YGX0
	AKAP3	ENST00000545990.6	TSL:2	c.		exon_region	Exon 6 of 6	ENSP00000440994.1	O75969

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.65

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr12-4724994;