16-53494145-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_022476.4(AKTIP):c.703G>A(p.Ala235Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00414 in 1,612,276 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0043 ( 20 hom. )

Consequence

AKTIP
NM_022476.4 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 7.77

Publications

5 publications found

Variant links:

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]

AKTIP links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.018119693).

BP6

Variant 16-53494145-C-T is Benign according to our data. Variant chr16-53494145-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 725925.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 396 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022476.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
AKTIP	NM_022476.4	MANE Select	c.703G>A	p.Ala235Thr	missense	Exon 8 of 10	NP_071921.1	Q9H8T0-1
AKTIP	NM_001308325.2		c.703G>A	p.Ala235Thr	missense	Exon 8 of 10	NP_001295254.1	Q9H8T0-2
AKTIP	NM_001012398.3		c.703G>A	p.Ala235Thr	missense	Exon 8 of 10	NP_001012398.1	Q9H8T0-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
AKTIP	ENST00000394657.12	TSL:2 MANE Select	c.703G>A	p.Ala235Thr	missense	Exon 8 of 10	ENSP00000378152.6	Q9H8T0-1
AKTIP	ENST00000570004.5	TSL:1	c.703G>A	p.Ala235Thr	missense	Exon 8 of 10	ENSP00000455874.1	Q9H8T0-1
AKTIP	ENST00000895076.1		c.832G>A	p.Ala278Thr	missense	Exon 9 of 11	ENSP00000565135.1

Frequencies

GnomAD3 genomes

AF:

0.00260

AC:

396

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000844

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000851

Gnomad ASJ

AF:

0.00692

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.00217

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00429

Gnomad OTH

AF:

0.00144

GnomAD2 exomes

AF:

0.00265

AC:

666

AN:

251434

AF XY:

0.00265

show subpopulations

Gnomad AFR exome

AF:

0.000554

Gnomad AMR exome

AF:

0.000954

Gnomad ASJ exome

AF:

0.00446

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.00342

Gnomad NFE exome

AF:

0.00391

Gnomad OTH exome

AF:

0.00293

GnomAD4 exome

AF:

0.00430

AC:

6276

AN:

1459984

Hom.:

Cov.:

AF XY:

0.00415

AC XY:

3018

AN XY:

726424

show subpopulations

African (AFR)

AF:

0.000599

AC:

AN:

33414

American (AMR)

AF:

0.000962

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00490

AC:

128

AN:

26120

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39682

South Asian (SAS)

AF:

0.00122

AC:

105

AN:

86234

European-Finnish (FIN)

AF:

0.00320

AC:

171

AN:

53418

Middle Eastern (MID)

AF:

0.000523

AC:

AN:

5732

European-Non Finnish (NFE)

AF:

0.00499

AC:

5544

AN:

1110324

Other (OTH)

AF:

0.00433

AC:

261

AN:

60340

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

278

557

835

1114

1392

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

228

456

684

912

1140

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00260

AC:

396

AN:

152292

Hom.:

Cov.:

AF XY:

0.00247

AC XY:

184

AN XY:

74472

show subpopulations

African (AFR)

AF:

0.000842

AC:

AN:

41570

American (AMR)

AF:

0.000850

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00692

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00124

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00217

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00429

AC:

292

AN:

68020

Other (OTH)

AF:

0.00142

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

102

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00357

Hom.:

Bravo

AF:

0.00227

TwinsUK

AF:

0.00836

AC:

ALSPAC

AF:

0.00441

AC:

ESP6500AA

AF:

0.000910

AC:

ESP6500EA

AF:

0.00616

AC:

ExAC

AF:

0.00251

AC:

305

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00458

EpiControl

AF:

0.00421

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.59

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Uncertain

0.070

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.11

Eigen

Uncertain

0.63

Eigen_PC

Pathogenic

0.67

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.95

M_CAP

Uncertain

0.097

MetaRNN

Benign

0.018

MetaSVM

Uncertain

0.084

MutationAssessor

Uncertain

2.7

PhyloP100

7.8

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-1.4

REVEL

Uncertain

0.60

Sift

Benign

0.20

Sift4G

Benign

0.36

Polyphen

0.66

Vest4

0.82

MVP

0.75

MPC

1.5

ClinPred

0.026

GERP RS

5.5

Varity_R

0.15

gMVP

0.59

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over