chrX-50192568-G-A

Variant names:

• chrX-50192568-G-A
• rs782053667
• NM_003886.3:c.2145C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_003886.3(AKAP4):​c.2145C>T​(p.Ser715Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000911 in 1,098,087 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 9.1e-7 (0 hom. 0 hem.)
• Consequence: AKAP4 NM_003886.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.78
• 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 -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP7: Synonymous conserved (PhyloP=2.78 with no splicing effect.

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.2145C>T	p.Ser715Ser	synonymous	Exon 5 of 6	NP_003877.2
	AKAP4	NM_139289.2		c.2118C>T	p.Ser706Ser	synonymous	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.2145C>T	p.Ser715Ser	synonymous	Exon 5 of 6	ENSP00000351327.2	Q5JQC9-1
	AKAP4	ENST00000376064.7	TSL:1	c.2118C>T	p.Ser706Ser	synonymous	Exon 5 of 6	ENSP00000365232.3	Q5JQC9-2
	AKAP4	ENST00000481402.5	TSL:1	n.2257C>T		non_coding_transcript_exon	Exon 5 of 6

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD2 exomes AF: 0.00000548 AC: 1 AN: 182404 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000722

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 9.11e-7 AC: 1 AN: 1098087 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 363465

African (AFR) AF: 0.00 AC: 0 AN: 26399

American (AMR) AF: 0.00 AC: 0 AN: 35196

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19381

East Asian (EAS) AF: 0.0000331 AC: 1 AN: 30203

South Asian (SAS) AF: 0.00 AC: 0 AN: 54136

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40430

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4136

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 842112

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

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	1.6
DANN	Benign	0.42
PhyloP100		2.8

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: rs782053667; hg19: chrX-49957219;