chrX-50190983-C-T

Variant names:

• chrX-50190983-C-T
• rs142609603
• NM_003886.3:c.2542G>A

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4 BS2

The NM_003886.3(AKAP4):​c.2542G>A​(p.Asp848Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000306 in 1,208,210 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 10 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00021 (0 hom., 7 hem., cov: 22)
  • Exomes 𝑓: 0.000013 (0 hom. 3 hem.)
• Consequence: AKAP4 NM_003886.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.05
• 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: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.37145913).
• BS2: High Hemizygotes in GnomAd4 at 7 gene

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.2542G>A	p.Asp848Asn	missense	Exon 6 of 6	NP_003877.2
	AKAP4	NM_139289.2		c.2515G>A	p.Asp839Asn	missense	Exon 6 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.2542G>A	p.Asp848Asn	missense	Exon 6 of 6	ENSP00000351327.2	Q5JQC9-1
	AKAP4	ENST00000376064.7	TSL:1	c.2515G>A	p.Asp839Asn	missense	Exon 6 of 6	ENSP00000365232.3	Q5JQC9-2
	AKAP4	ENST00000481402.5	TSL:1	n.2654G>A		non_coding_transcript_exon	Exon 6 of 6

Frequencies

GnomAD3 genomes AF: 0.000209 AC: 23 AN: 110173 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.000761

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

GnomAD2 exomes AF: 0.0000494 AC: 9 AN: 182134 AF XY: 0.0000447

Gnomad AFR exome AF: 0.000684

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000127 AC: 14 AN: 1098037 Hom.: 0 Cov.: 30 AF XY: 0.00000825 AC XY: 3 AN XY: 363451

African (AFR) AF: 0.000455 AC: 12 AN: 26392

American (AMR) AF: 0.00 AC: 0 AN: 35191

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19370

East Asian (EAS) AF: 0.0000331 AC: 1 AN: 30201

South Asian (SAS) AF: 0.00 AC: 0 AN: 54114

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40518

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4131

European-Non Finnish (NFE) AF: 0.00000119 AC: 1 AN: 842026

Other (OTH) AF: 0.00 AC: 0 AN: 46094

GnomAD4 genome AF: 0.000209 AC: 23 AN: 110173 Hom.: 0 Cov.: 22 AF XY: 0.000216 AC XY: 7 AN XY: 32453

African (AFR) AF: 0.000761 AC: 23 AN: 30229

American (AMR) AF: 0.00 AC: 0 AN: 10251

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2622

East Asian (EAS) AF: 0.00 AC: 0 AN: 3529

South Asian (SAS) AF: 0.00 AC: 0 AN: 2486

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5827

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 52829

Other (OTH) AF: 0.00 AC: 0 AN: 1476

Alfa AF: 0.000285 Hom.: 1

Bravo AF: 0.000329

ESP6500AA AF: 0.00104 AC: 4

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000577 AC: 7

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	Uncertain	0.43
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.33	T
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.025	D
MetaRNN	Benign	0.37	T
MetaSVM	Benign	-0.87	T
MutationAssessor	Uncertain	2.9	M
PhyloP100		4.0
PrimateAI	Uncertain	0.49	T
PROVEAN	Uncertain	-4.3	D
REVEL	Benign	0.22
Sift	Uncertain	0.0030	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.49
MVP		0.63
MPC		0.62
ClinPred		0.57	D
GERP RS		4.6
Varity_R		0.59
gMVP		0.96
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: rs142609603; hg19: chrX-49955626;