16-53493869-G-T

Variant names:

• chr16-53493869-G-T
• rs9302648
• NM_022476.4:c.710+269C>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 15 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
AKTIP	NM_022476.4	c.710+269C>A		intron_variant	Intron 8 of 9	ENST00000394657.12	NP_071921.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AKTIP	ENST00000394657.12	c.710+269C>A		intron_variant	Intron 8 of 9	2	NM_022476.4	ENSP00000378152.6
AKTIP	ENST00000570004.5	c.710+269C>A		intron_variant	Intron 8 of 9	1		ENSP00000455874.1
AKTIP	ENST00000571523.2	n.100C>A		non_coding_transcript_exon_variant	Exon 1 of 1	6
AKTIP	ENST00000300245.8	c.710+269C>A		intron_variant	Intron 9 of 10	5		ENSP00000300245.4

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

African (AFR) AF: 0.779 AC: 7325 AN: 9402

American (AMR) AF: 0.367 AC: 4173 AN: 11356

Ashkenazi Jewish (ASJ) AF: 0.587 AC: 5413 AN: 9216

East Asian (EAS) AF: 0.170 AC: 3465 AN: 20342

South Asian (SAS) AF: 0.489 AC: 11009 AN: 22520

European-Finnish (FIN) AF: 0.349 AC: 5403 AN: 15480

Middle Eastern (MID) AF: 0.594 AC: 733 AN: 1234

European-Non Finnish (NFE) AF: 0.463 AC: 79069 AN: 170906

Other (OTH) AF: 0.490 AC: 8247 AN: 16836

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

African (AFR) AF: 0.780 AC: 32341 AN: 41476

American (AMR) AF: 0.438 AC: 6692 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.588 AC: 2038 AN: 3466

East Asian (EAS) AF: 0.180 AC: 933 AN: 5180

South Asian (SAS) AF: 0.465 AC: 2240 AN: 4816

European-Finnish (FIN) AF: 0.338 AC: 3557 AN: 10528

Middle Eastern (MID) AF: 0.656 AC: 193 AN: 294

European-Non Finnish (NFE) AF: 0.458 AC: 31150 AN: 67986

Other (OTH) AF: 0.545 AC: 1150 AN: 2112

Alfa AF: 0.423 Hom.: 1985

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
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

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: rs9302648; hg19: chr16-53527781;