chr16-53493869-G-T

Position:

• chr16-53493869-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022476.4(AKTIP):​c.710+269C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.479 in 429,328 control chromosomes in the GnomAD database, including 53,977 homozygotes. 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: 𝑓 0.53 (23649 hom., cov: 33)
  • Exomes 𝑓: 0.45 (30328 hom.)
• Consequence: AKTIP NM_022476.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08

Genes affected

AKTIP (HGNC:16710): (AKT interacting protein) The mouse homolog of this gene produces fused toes and thymic hyperplasia in heterozygous mutant animals while homozygous mutants die in early development. This gene may play a role in apoptosis as these morphological abnormalities are caused by altered patterns of programmed cell death. The protein encoded by this gene is similar to the ubiquitin ligase domain of other ubiquitin-conjugating enzymes but lacks the conserved cysteine residue that enables those enzymes to conjugate ubiquitin to the target protein. This protein interacts directly with serine/threonine kinase protein kinase B (PKB)/Akt and modulates PKB activity by enhancing the phosphorylation of PKB's regulatory sites. Alternative splicing results in two transcript variants encoding the same protein. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.773 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AKTIP	NM_022476.4	c.710+269C>A		intron_variant		ENST00000394657.12	NP_071921.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AKTIP	ENST00000394657.12	c.710+269C>A		intron_variant		2	NM_022476.4	ENSP00000378152	P4
AKTIP	ENST00000570004.5	c.710+269C>A		intron_variant		1		ENSP00000455874	P4
AKTIP	ENST00000300245.8	c.710+269C>A		intron_variant		5		ENSP00000300245	A1
AKTIP	ENST00000571523.2	n.100C>A		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.530 AC: 80573 AN: 151918 Hom.: 23605 Cov.: 33

Gnomad AFR AF: 0.780

Gnomad AMI AF: 0.414

Gnomad AMR AF: 0.439

Gnomad ASJ AF: 0.588

Gnomad EAS AF: 0.180

Gnomad SAS AF: 0.466

Gnomad FIN AF: 0.338

Gnomad MID AF: 0.642

Gnomad NFE AF: 0.458

Gnomad OTH AF: 0.540

GnomAD4 exome AF: 0.450 AC: 124837 AN: 277292 Hom.: 30328 Cov.: 0 AF XY: 0.453 AC XY: 65182 AN XY: 144012

Gnomad4 AFR exome AF: 0.779

Gnomad4 AMR exome AF: 0.367

Gnomad4 ASJ exome AF: 0.587

Gnomad4 EAS exome AF: 0.170

Gnomad4 SAS exome AF: 0.489

Gnomad4 FIN exome AF: 0.349

Gnomad4 NFE exome AF: 0.463

Gnomad4 OTH exome AF: 0.490

GnomAD4 genome AF: 0.531 AC: 80670 AN: 152036 Hom.: 23649 Cov.: 33 AF XY: 0.521 AC XY: 38709 AN XY: 74314

Gnomad4 AFR AF: 0.780

Gnomad4 AMR AF: 0.438

Gnomad4 ASJ AF: 0.588

Gnomad4 EAS AF: 0.180

Gnomad4 SAS AF: 0.465

Gnomad4 FIN AF: 0.338

Gnomad4 NFE AF: 0.458

Gnomad4 OTH AF: 0.545

Alfa AF: 0.406 Hom.: 1734

Bravo AF: 0.544

Asia WGS AF: 0.423 AC: 1475 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.63
DANN	Benign	0.69

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: rs9302648; hg19: chr16-53527781;