13-42297145-A-G

Position:

• chr13-42297145-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The ENST00000025301.4(AKAP11):​c.314A>G​(p.Asn105Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00103 in 1,570,850 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0056 (10 hom., cov: 32)
  • Exomes 𝑓: 0.00054 (4 hom.)
• Consequence: AKAP11 ENST00000025301.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.56

Genes affected

AKAP11 (HGNC:369): (A-kinase anchoring protein 11) 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 expressed at high levels throughout spermatogenesis and in mature sperm. It binds the RI and RII subunits of PKA in testis. It may serve a function in cell cycle control of both somatic cells and germ cells in addition to its putative role in spermatogenesis and sperm function. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.00310269).
• BP6: Variant 13-42297145-A-G is Benign according to our data. Variant chr13-42297145-A-G is described in ClinVar as [Benign]. Clinvar id is 709272.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00563 (857/152108) while in subpopulation AFR AF= 0.019 (788/41576). AF 95% confidence interval is 0.0179. There are 10 homozygotes in gnomad4. There are 408 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 10 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AKAP11	NM_016248.4	c.314A>G	p.Asn105Ser	missense_variant	6/13	ENST00000025301.4	NP_057332.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AKAP11	ENST00000025301.4	c.314A>G	p.Asn105Ser	missense_variant	6/13	1	NM_016248.4	ENSP00000025301.2

Frequencies

GnomAD3 genomes AF: 0.00564 AC: 857 AN: 151990 Hom.: 10 Cov.: 32

Gnomad AFR AF: 0.0190

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00360

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00191

GnomAD3 exomes AF: 0.00134 AC: 300 AN: 224096 Hom.: 6 AF XY: 0.00105 AC XY: 128 AN XY: 122378

Gnomad AFR exome AF: 0.0184

Gnomad AMR exome AF: 0.000996

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000470

Gnomad NFE exome AF: 0.000172

Gnomad OTH exome AF: 0.000770

GnomAD4 exome AF: 0.000539 AC: 764 AN: 1418742 Hom.: 4 Cov.: 27 AF XY: 0.000419 AC XY: 296 AN XY: 706370

Gnomad4 AFR exome AF: 0.0184

Gnomad4 AMR exome AF: 0.00106

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000374

Gnomad4 FIN exome AF: 0.0000189

Gnomad4 NFE exome AF: 0.0000533

Gnomad4 OTH exome AF: 0.00119

GnomAD4 genome AF: 0.00563 AC: 857 AN: 152108 Hom.: 10 Cov.: 32 AF XY: 0.00549 AC XY: 408 AN XY: 74348

Gnomad4 AFR AF: 0.0190

Gnomad4 AMR AF: 0.00360

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000118

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.000957 Hom.: 2

Bravo AF: 0.00605

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.0130 AC: 57

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00180 AC: 218

Asia WGS AF: 0.00174 AC: 6 AN: 3468

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 10, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.062
BayesDel_addAF	Benign	-0.71	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	13
DANN	Benign	0.89
DEOGEN2	Benign	0.0027	T
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.44
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.74	T
MetaRNN	Benign	0.0031	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.77	N
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.52	N
REVEL	Benign	0.070
Sift	Benign	0.43	T
Sift4G	Benign	0.86	T
Polyphen		0.023	B
Vest4		0.061
MVP		0.19
MPC		0.043
ClinPred		0.0013	T
GERP RS		2.1
Varity_R		0.030
gMVP		0.084

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: rs114345660; hg19: chr13-42871281;