Variant 6-109506403-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001145128.3(AK9):c.4773G>T(p.Trp1591Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00375 in 1,613,660 control chromosomes in the GnomAD database, including 196 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.021 ( 101 hom., cov: 32)

Exomes 𝑓: 0.0020 ( 95 hom. )

Consequence

AK9
NM_001145128.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.52

Variant links:

Genes affected

AK9 (HGNC:33814): (adenylate kinase 9) The protein encoded by this gene catalyzes the interconversion of nucleosides, possessing both nucleoside monophosphate and diphosphate kinase activities. The encoded protein uses these interconversions to maintain nucleoside homeostasis. [provided by RefSeq, Jul 2016]

AK9 links:

ZBTB24-DT (HGNC:55872): (ZBTB24 divergent transcript)

ZBTB24-DT links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007969171).

BP6

Variant 6-109506403-C-A is Benign according to our data. Variant chr6-109506403-C-A is described in ClinVar as [Benign]. Clinvar id is 770553.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.071 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AK9	NM_001145128.3 linkuse as main transcript	c.4773G>T	p.Trp1591Cys	missense_variant	35/41	ENST00000424296.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AK9	ENST00000424296.7 linkuse as main transcript	c.4773G>T	p.Trp1591Cys	missense_variant	35/41	5	NM_001145128.3	P1	Q5TCS8-4
ZBTB24-DT	ENST00000658720.1 linkuse as main transcript	n.1429-274C>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.0208

AC:

3154

AN:

151988

Hom.:

101

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0732

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00570

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.0129

GnomAD3 exomes

AF:

0.00528

AC:

1327

AN:

251272

Hom.:

AF XY:

0.00370

AC XY:

502

AN XY:

135824

show subpopulations

Gnomad AFR exome

AF:

0.0750

Gnomad AMR exome

AF:

0.00234

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000229

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000792

Gnomad OTH exome

AF:

0.00196

GnomAD4 exome

AF:

0.00197

AC:

2883

AN:

1461554

Hom.:

Cov.:

AF XY:

0.00171

AC XY:

1246

AN XY:

727078

show subpopulations

Gnomad4 AFR exome

AF:

0.0732

Gnomad4 AMR exome

AF:

0.00262

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000197

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000387

Gnomad4 OTH exome

AF:

0.00406

GnomAD4 genome

AF:

0.0208

AC:

3161

AN:

152106

Hom.:

101

Cov.:

AF XY:

0.0200

AC XY:

1489

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.0732

Gnomad4 AMR

AF:

0.00569

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000191

Gnomad4 OTH

AF:

0.0128

Alfa

AF:

0.00366

Hom.:

Bravo

AF:

0.0235

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.0685

AC:

302

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00656

AC:

797

Asia WGS

AF:

0.00376

AC:

AN:

3476

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Oct 09, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.66

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.17

Cadd

Pathogenic

Dann

Uncertain

0.98

DEOGEN2

Benign

0.052

Eigen

Uncertain

0.65

Eigen_PC

Uncertain

0.62

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.81

MetaRNN

Benign

0.0080

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.6

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.55

PROVEAN

Pathogenic

-8.1

REVEL

Benign

0.28

Sift

Benign

0.11

Sift4G

Uncertain

0.0050

Polyphen

1.0

Vest4

0.83

MutPred

0.54

Loss of MoRF binding (P = 0.0186);

MVP

0.43

MPC

0.75

ClinPred

0.047

GERP RS

4.8

Varity_R

0.55

gMVP

0.67

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over