chrX-50192663-C-G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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.

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

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AKAP4	NM_003886.3	c.2050G>C	p.Asp684His	missense_variant	Exon 5 of 6	ENST00000358526.7	NP_003877.2
AKAP4	NM_139289.2	c.2023G>C	p.Asp675His	missense_variant	Exon 5 of 6		NP_647450.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AKAP4	ENST00000358526.7	c.2050G>C	p.Asp684His	missense_variant	Exon 5 of 6	1	NM_003886.3	ENSP00000351327.2
AKAP4	ENST00000376064.7	c.2023G>C	p.Asp675His	missense_variant	Exon 5 of 6	1		ENSP00000365232.3
AKAP4	ENST00000481402.5	n.2162G>C		non_coding_transcript_exon_variant	Exon 5 of 6	1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 22

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.31	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.6	M;.
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-2.1	N;N
REVEL	Benign	0.26
Sift	Uncertain	0.022	D;D
Sift4G	Benign	0.13	T;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

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: rs191821579; hg19: chrX-49957314;