12-4626614-TTG-T

Position:

• chr12-4626614-TTG-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP5

The NM_001278309.2(AKAP3):​c.2286_2287del​(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).

• 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

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 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 id is 2500165.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr12-4626614-TTG-T is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AKAP3	NM_001278309.2	c.2286_2287del	p.His762GlnfsTer22	frameshift_variant	5/6	ENST00000228850.6	NP_001265238.2
AKAP3	NM_006422.4	c.2286_2287del	p.His762GlnfsTer22	frameshift_variant	5/6		NP_006413.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AKAP3	ENST00000228850.6	c.2286_2287del	p.His762GlnfsTer22	frameshift_variant	5/6	5	NM_001278309.2	ENSP00000228850	P1
AKAP3	ENST00000545990.6	c.2286_2287del	p.His762GlnfsTer22	frameshift_variant	5/6	2		ENSP00000440994	P1

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

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Spermatogenic failure 82 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Dec 14, 2023

- -

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs1220814973; hg19: chr12-4735780;