rs1486445723

Variant names:

• chrX-50192935-G-A
• rs1486445723
• NM_003886.3:c.1778C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003886.3(AKAP4):​c.1778C>T​(p.Ala593Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000358 in 111,746 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.000036 (0 hom., 0 hem., cov: 22)
• Consequence: AKAP4 NM_003886.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.96
• Publications: 0 publications found

Genes affected

AKAP4 (HGNC:374): (A-kinase anchoring protein 4) The A-kinase anchor proteins (AKAPs) are a group of structurally diverse proteins, which have the common function of binding to the regulatory subunit of protein kinase A (PKA) and confining the holoenzyme to discrete locations within the cell. This gene encodes a member of the AKAP family. The encoded protein is localized to the sperm flagellum and may be involved in the regulation of sperm motility. Alternative splicing of this gene results in two transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

ENSG00000301433 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17179903).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003886.3. 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
	AKAP4	NM_003886.3	MANE Select	c.1778C>T	p.Ala593Val	missense	Exon 5 of 6	NP_003877.2
	AKAP4	NM_139289.2		c.1751C>T	p.Ala584Val	missense	Exon 5 of 6	NP_647450.1	Q5JQC9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AKAP4	ENST00000358526.7	TSL:1 MANE Select	c.1778C>T	p.Ala593Val	missense	Exon 5 of 6	ENSP00000351327.2	Q5JQC9-1
	AKAP4	ENST00000376064.7	TSL:1	c.1751C>T	p.Ala584Val	missense	Exon 5 of 6	ENSP00000365232.3	Q5JQC9-2
	AKAP4	ENST00000481402.5	TSL:1	n.1890C>T		non_coding_transcript_exon	Exon 5 of 6

Frequencies

GnomAD3 genomes AF: 0.0000358 AC: 4 AN: 111746 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.000130

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome AF: 0.0000358 AC: 4 AN: 111746 Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0 AN XY: 33916

African (AFR) AF: 0.000130 AC: 4 AN: 30703

American (AMR) AF: 0.00 AC: 0 AN: 10538

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2645

East Asian (EAS) AF: 0.00 AC: 0 AN: 3544

South Asian (SAS) AF: 0.00 AC: 0 AN: 2668

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6081

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 239

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53131

Other (OTH) AF: 0.00 AC: 0 AN: 1513

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	12
DANN	Uncertain	1.0
DEOGEN2	Benign	0.095	T
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.0094	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		3.0
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.078
Sift	Uncertain	0.021	D
Sift4G	Benign	0.38	T
Polyphen		0.0050	B
Vest4		0.097
MutPred		0.53		Gain of methylation at K594 (P = 0.0531)
MVP		0.35
MPC		0.15
ClinPred		0.23	T
GERP RS		3.1
Varity_R		0.13
gMVP		0.099
Mutation Taster		=93/7	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: rs1486445723; hg19: chrX-49957586;