NM_003886.3:c.2050G>C

Variant names:

• chrX-50192663-C-G
• rs191821579
• NM_003886.3:c.2050G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_003886.3(AKAP4):​c.2050G>C​(p.Asp684His) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D684N) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 22)
• Consequence: AKAP4 NM_003886.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.45
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3146233).

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.2050G>C	p.Asp684His	missense	Exon 5 of 6	NP_003877.2
	AKAP4	NM_139289.2		c.2023G>C	p.Asp675His	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.2050G>C	p.Asp684His	missense	Exon 5 of 6	ENSP00000351327.2	Q5JQC9-1
	AKAP4	ENST00000376064.7	TSL:1	c.2023G>C	p.Asp675His	missense	Exon 5 of 6	ENSP00000365232.3	Q5JQC9-2
	AKAP4	ENST00000481402.5	TSL:1	n.2162G>C		non_coding_transcript_exon	Exon 5 of 6

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 22

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.23	T
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		1.4
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.26
Sift	Uncertain	0.022	D
Sift4G	Benign	0.13	T
Polyphen		1.0	D
Vest4		0.45
MutPred		0.50		Loss of loop (P = 0.0128)
MVP		0.71
MPC		0.68
ClinPred		0.93	D
GERP RS		5.1
Varity_R		0.30
gMVP		0.67
Mutation Taster		=92/8	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: rs191821579; hg19: chrX-49957314;