Variant 6-109506743-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001145128.3(AK9):c.4539G>T(p.Arg1513Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000726 in 1,377,748 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.3e-7 ( 0 hom. )

Consequence

AK9
NM_001145128.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.618

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.22748944).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AK9	NM_001145128.3 linkuse as main transcript	c.4539G>T	p.Arg1513Ser	missense_variant	34/41	ENST00000424296.7	NP_001138600.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AK9	ENST00000424296.7 linkuse as main transcript	c.4539G>T	p.Arg1513Ser	missense_variant	34/41	5	NM_001145128.3	ENSP00000410186	P1	Q5TCS8-4
ZBTB24-DT	ENST00000658720.1 linkuse as main transcript	n.1495C>A		non_coding_transcript_exon_variant	4/4
AK9	ENST00000470564.5 linkuse as main transcript	c.1053G>T	p.Arg351Ser	missense_variant	7/14	5		ENSP00000418771
ZBTB24-DT	ENST00000423747.2 linkuse as main transcript	n.325C>A		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000655

AC:

AN:

152762

Hom.:

AF XY:

0.00

AC XY:

AN XY:

80724

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000420

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.26e-7

AC:

AN:

1377748

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

674682

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000290

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 27, 2023

The c.4539G>T (p.R1513S) alteration is located in exon 34 (coding exon 33) of the AK9 gene. This alteration results from a G to T substitution at nucleotide position 4539, causing the arginine (R) at amino acid position 1513 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.34

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.46

CADD

Benign

9.4

DANN

Uncertain

0.99

DEOGEN2

Benign

0.13

Eigen

Benign

-0.22

Eigen_PC

Benign

-0.32

FATHMM_MKL

Benign

0.27

LIST_S2

Benign

0.60

M_CAP

Benign

0.025

MetaRNN

Benign

0.23

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

MutationTaster

Benign

1.0

PrimateAI

Benign

0.42

PROVEAN

Benign

-2.3

REVEL

Benign

0.20

Sift

Benign

0.41

Sift4G

Benign

0.45

Polyphen

0.96

Vest4

0.44

MutPred

0.52

Loss of catalytic residue at R1513 (P = 0.1206);

MVP

0.25

MPC

0.40

ClinPred

0.49

GERP RS

0.91

Varity_R

0.23

gMVP

0.61

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

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