chr12-4626765-T-G

Variant names:

• chr12-4626765-T-G
• rs754852568
• NM_001278309.2:c.2137A>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001278309.2(AKAP3):​c.2137A>C​(p.Ser713Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: AKAP3 NM_001278309.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.93

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]

ENSG00000272921 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2090474).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AKAP3	NM_001278309.2	c.2137A>C	p.Ser713Arg	missense_variant	Exon 5 of 6	ENST00000228850.6	NP_001265238.2
AKAP3	NM_006422.4	c.2137A>C	p.Ser713Arg	missense_variant	Exon 5 of 6		NP_006413.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AKAP3	ENST00000228850.6	c.2137A>C	p.Ser713Arg	missense_variant	Exon 5 of 6	5	NM_001278309.2	ENSP00000228850.1
ENSG00000272921	ENST00000536588.1	n.142-4557T>G		intron_variant	Intron 1 of 6	3		ENSP00000445121.1
AKAP3	ENST00000545990.6	c.2137A>C	p.Ser713Arg	missense_variant	Exon 5 of 6	2		ENSP00000440994.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 64

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.012	T;T
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.42
FATHMM_MKL	Benign	0.091	N
LIST_S2	Benign	0.58	.;T
M_CAP	Benign	0.0051	T
MetaRNN	Benign	0.21	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.6	M;M
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.5	N;N
REVEL	Benign	0.068
Sift	Uncertain	0.0060	D;D
Sift4G	Benign	0.098	T;T
Polyphen		0.86	P;P
Vest4		0.20
MutPred		0.63		Loss of glycosylation at S713 (P = 0.0428);Loss of glycosylation at S713 (P = 0.0428);
MVP		0.42
MPC		0.44
ClinPred		0.60	D
GERP RS		3.7
Varity_R		0.18
gMVP		0.41

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

Publications

LitVar

Other links and lift over

dbSNP: rs754852568; hg19: chr12-4735931;