rs9400317

Variant names:

• chr6-109686444-A-G
• rs9400317
• NM_001145128.3:c.-12+4703T>C

Your query was ambiguous. Multiple possible variants found:

• chr6-109686444-A-G
• chr6-109686444-A-T

Variant summary

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

The NM_001145128.3(AK9):​c.-12+4703T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.911 in 152,284 control chromosomes in the GnomAD database, including 63,370 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 0.91 (63370 hom., cov: 32)
• Consequence: AK9 NM_001145128.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.114
• Publications: 17 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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145128.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AK9	NM_001145128.3	MANE Select	c.-12+4703T>C		intron	N/A	NP_001138600.2	Q5TCS8-4
	AK9	NM_001329603.2		c.-12-384T>C		intron	N/A	NP_001316532.1
	AK9	NM_001329602.2		c.-12+4028T>C		intron	N/A	NP_001316531.1	Q5TCS8-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AK9	ENST00000424296.7	TSL:5 MANE Select	c.-12+4703T>C		intron	N/A	ENSP00000410186.2	Q5TCS8-4
	AK9	ENST00000285397.9	TSL:1	c.-12+4703T>C		intron	N/A	ENSP00000285397.4	Q5TCS8-2
	AK9	ENST00000368948.6	TSL:5	c.-12+4703T>C		intron	N/A	ENSP00000357944.2	J3KP89

Frequencies

GnomAD3 genomes AF: 0.911 AC: 138586 AN: 152166 Hom.: 63309 Cov.: 32

Gnomad AFR AF: 0.980

Gnomad AMI AF: 0.866

Gnomad AMR AF: 0.915

Gnomad ASJ AF: 0.851

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.857

Gnomad FIN AF: 0.906

Gnomad MID AF: 0.832

Gnomad NFE AF: 0.870

Gnomad OTH AF: 0.886

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

GnomAD4 genome AF: 0.911 AC: 138705 AN: 152284 Hom.: 63370 Cov.: 32 AF XY: 0.912 AC XY: 67871 AN XY: 74448

African (AFR) AF: 0.980 AC: 40731 AN: 41576

American (AMR) AF: 0.915 AC: 14000 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.851 AC: 2956 AN: 3472

East Asian (EAS) AF: 0.999 AC: 5173 AN: 5176

South Asian (SAS) AF: 0.856 AC: 4131 AN: 4824

European-Finnish (FIN) AF: 0.906 AC: 9601 AN: 10602

Middle Eastern (MID) AF: 0.830 AC: 244 AN: 294

European-Non Finnish (NFE) AF: 0.870 AC: 59201 AN: 68018

Other (OTH) AF: 0.888 AC: 1880 AN: 2116

Alfa AF: 0.884 Hom.: 189271

Bravo AF: 0.917

Asia WGS AF: 0.950 AC: 3306 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	6.8
DANN	Benign	0.77
PhyloP100		0.11
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: rs9400317; hg19: chr6-110007647;