6-109641923-C-T

Variant names:

• chr6-109641923-C-T
• rs7745469
• NM_001145128.3:c.835-307G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001145128.3(AK9):​c.835-307G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.583 in 152,006 control chromosomes in the GnomAD database, including 27,493 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 0.58 (27493 hom., cov: 32)
• Consequence: AK9 NM_001145128.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.180
• Publications: 9 publications found

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 Gene-Disease associations (from GenCC):

• postsynaptic congenital myasthenic syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.822 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AK9	NM_001145128.3	c.835-307G>A		intron_variant	Intron 9 of 40	ENST00000424296.7	NP_001138600.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AK9	ENST00000424296.7	c.835-307G>A		intron_variant	Intron 9 of 40	5	NM_001145128.3	ENSP00000410186.2

Frequencies

GnomAD3 genomes AF: 0.583 AC: 88543 AN: 151888 Hom.: 27483 Cov.: 32

Gnomad AFR AF: 0.363

Gnomad AMI AF: 0.615

Gnomad AMR AF: 0.689

Gnomad ASJ AF: 0.727

Gnomad EAS AF: 0.843

Gnomad SAS AF: 0.842

Gnomad FIN AF: 0.687

Gnomad MID AF: 0.712

Gnomad NFE AF: 0.629

Gnomad OTH AF: 0.616

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.583 AC: 88589 AN: 152006 Hom.: 27493 Cov.: 32 AF XY: 0.593 AC XY: 44078 AN XY: 74308

African (AFR) AF: 0.363 AC: 15033 AN: 41446

American (AMR) AF: 0.690 AC: 10526 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.727 AC: 2523 AN: 3470

East Asian (EAS) AF: 0.843 AC: 4356 AN: 5168

South Asian (SAS) AF: 0.844 AC: 4066 AN: 4820

European-Finnish (FIN) AF: 0.687 AC: 7260 AN: 10566

Middle Eastern (MID) AF: 0.714 AC: 210 AN: 294

European-Non Finnish (NFE) AF: 0.629 AC: 42755 AN: 67962

Other (OTH) AF: 0.618 AC: 1300 AN: 2104

Alfa AF: 0.494 Hom.: 1883

Bravo AF: 0.571

Asia WGS AF: 0.811 AC: 2817 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.5
DANN	Benign	0.21
PhyloP100		-0.18
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: rs7745469; hg19: chr6-109963126;