Genetic Variant AGK:c.-15+31C>G (chr7-141551465-C-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_018238.4(AGK):c.-15+31C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0913 in 153,246 control chromosomes in the GnomAD database, including 1,400 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.092 ( 1399 hom., cov: 33)

Exomes 𝑓: 0.038 ( 1 hom. )

Consequence

AGK
NM_018238.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.180

Publications

2 publications found

Variant links:

Genes affected

AGK (HGNC:21869): (acylglycerol kinase) The protein encoded by this gene is a mitochondrial membrane protein involved in lipid and glycerolipid metabolism. The encoded protein is a lipid kinase that catalyzes the formation of phosphatidic and lysophosphatidic acids. Defects in this gene have been associated with mitochondrial DNA depletion syndrome 10. [provided by RefSeq, Feb 2012]

AGK links:

AGK-DT (HGNC:55356): (AGK divergent transcript)

AGK-DT links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 7-141551465-C-G is Benign according to our data. Variant chr7-141551465-C-G is described in ClinVar as Benign. ClinVar VariationId is 1329573.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.243 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018238.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
AGK	NM_018238.4	MANE Select	c.-15+31C>G	intron	N/A	NP_060708.1	Q53H12-1
AGK	NM_001364948.3		c.-15+31C>G	intron	N/A	NP_001351877.1	A0A3B3ISZ0
AGK-DT	NR_183402.1		n.-121G>C	upstream_gene	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
AGK	ENST00000649286.2	MANE Select	c.-15+31C>G	intron	N/A	ENSP00000497280.1	Q53H12-1
AGK	ENST00000912226.1		c.-16C>G	splice_region	Exon 1 of 16	ENSP00000582285.1
AGK	ENST00000648068.1		c.-49C>G	5_prime_UTR	Exon 1 of 16	ENSP00000498112.1	Q53H12-1

Frequencies

GnomAD3 genomes

AF:

0.0913

AC:

13896

AN:

152166

Hom.:

1389

Cov.:

show subpopulations

Gnomad AFR

AF:

0.246

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.0432

Gnomad ASJ

AF:

0.0187

Gnomad EAS

AF:

0.0378

Gnomad SAS

AF:

0.149

Gnomad FIN

AF:

0.0127

Gnomad MID

AF:

0.0287

Gnomad NFE

AF:

0.0258

Gnomad OTH

AF:

0.0731

GnomAD4 exome

AF:

0.0381

AC:

AN:

970

Hom.:

Cov.:

AF XY:

0.0372

AC XY:

AN XY:

726

show subpopulations

African (AFR)

AF:

0.167

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.100

AC:

AN:

South Asian (SAS)

AF:

0.0909

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AF:

0.250

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0303

AC:

AN:

824

Other (OTH)

AF:

0.105

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0916

AC:

13955

AN:

152276

Hom.:

1399

Cov.:

AF XY:

0.0908

AC XY:

6758

AN XY:

74468

show subpopulations

African (AFR)

AF:

0.247

AC:

10255

AN:

41530

American (AMR)

AF:

0.0435

AC:

665

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0187

AC:

AN:

3470

East Asian (EAS)

AF:

0.0379

AC:

196

AN:

5176

South Asian (SAS)

AF:

0.150

AC:

723

AN:

4828

European-Finnish (FIN)

AF:

0.0127

AC:

135

AN:

10628

Middle Eastern (MID)

AF:

0.0274

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0258

AC:

1752

AN:

68020

Other (OTH)

AF:

0.0723

AC:

153

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

572

1144

1717

2289

2861

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

154

308

462

616

770

<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:

0.0625

Hom.:

Bravo

AF:

0.100

Asia WGS

AF:

0.109

AC:

377

AN:

3470

ClinVar

ClinVar submissions

Significance: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

BayesDel_noAF

Benign

-0.90

CADD

Benign

5.8

(source)

DANN

Benign

0.34

PhyloP100

-0.18

PromoterAI

0.069

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over