chr12-4615829-C-T

Variant names:

• chr12-4615829-C-T
• rs34215645
• NM_001278309.2:c.2472G>A

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_001278309.2(AKAP3):​c.2472G>A​(p.Val824Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00968 in 1,614,222 control chromosomes in the GnomAD database, including 95 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0071 (4 hom., cov: 33)
  • Exomes 𝑓: 0.010 (91 hom.)
• Consequence: AKAP3 NM_001278309.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.647
• Publications: 3 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: Benign. The variant received -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP6: Variant 12-4615829-C-T is Benign according to our data. Variant chr12-4615829-C-T is described in ClinVar as Benign. ClinVar VariationId is 720004.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.647 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 4 Unknown gene

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.2472G>A	p.Val824Val	synonymous	Exon 6 of 6	NP_001265238.2	O75969
	AKAP3	NM_006422.4		c.2472G>A	p.Val824Val	synonymous	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.2472G>A	p.Val824Val	synonymous	Exon 6 of 6	ENSP00000228850.1	O75969
	ENSG00000272921	ENST00000536588.1	TSL:3	n.141+10743C>T		intron	N/A	ENSP00000445121.1	H0YGX0
	AKAP3	ENST00000545990.6	TSL:2	c.2472G>A	p.Val824Val	synonymous	Exon 6 of 6	ENSP00000440994.1	O75969

Frequencies

GnomAD3 genomes AF: 0.00706 AC: 1075 AN: 152234 Hom.: 4 Cov.: 33

Gnomad AFR AF: 0.00183

Gnomad AMI AF: 0.0296

Gnomad AMR AF: 0.00877

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00245

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0116

Gnomad OTH AF: 0.00621

GnomAD2 exomes AF: 0.00626 AC: 1571 AN: 250946 AF XY: 0.00637

Gnomad AFR exome AF: 0.00123

Gnomad AMR exome AF: 0.00555

Gnomad ASJ exome AF: 0.00308

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00263

Gnomad NFE exome AF: 0.0107

Gnomad OTH exome AF: 0.00751

GnomAD4 exome AF: 0.00995 AC: 14551 AN: 1461870 Hom.: 91 Cov.: 31 AF XY: 0.00957 AC XY: 6962 AN XY: 727240

African (AFR) AF: 0.00155 AC: 52 AN: 33478

American (AMR) AF: 0.00568 AC: 254 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00260 AC: 68 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.000348 AC: 30 AN: 86258

European-Finnish (FIN) AF: 0.00320 AC: 171 AN: 53418

Middle Eastern (MID) AF: 0.00329 AC: 19 AN: 5768

European-Non Finnish (NFE) AF: 0.0121 AC: 13484 AN: 1112002

Other (OTH) AF: 0.00783 AC: 473 AN: 60396

GnomAD4 genome AF: 0.00706 AC: 1075 AN: 152352 Hom.: 4 Cov.: 33 AF XY: 0.00703 AC XY: 524 AN XY: 74504

African (AFR) AF: 0.00183 AC: 76 AN: 41584

American (AMR) AF: 0.00869 AC: 133 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00144 AC: 5 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5178

South Asian (SAS) AF: 0.000828 AC: 4 AN: 4830

European-Finnish (FIN) AF: 0.00245 AC: 26 AN: 10630

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0116 AC: 788 AN: 68034

Other (OTH) AF: 0.00614 AC: 13 AN: 2116

Alfa AF: 0.00878 Hom.: 4

Bravo AF: 0.00660

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.0116

EpiControl AF: 0.0106

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	0.72
DANN	Benign	0.69
PhyloP100		-0.65
Mutation Taster		=100/0	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: rs34215645; hg19: chr12-4724995;