7-141555483-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_018238.4(AGK):c.17A>G(p.Lys6Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000924 in 1,614,026 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0022 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00079 ( 8 hom. )

Consequence

AGK
NM_018238.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 1.59

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0059469044).

BP6

Variant 7-141555483-A-G is Benign according to our data. Variant chr7-141555483-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 214064.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-141555483-A-G is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00222 (338/152328) while in subpopulation AFR AF= 0.00551 (229/41570). AF 95% confidence interval is 0.00492. There are 1 homozygotes in gnomad4. There are 142 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
AGK	NM_018238.4 linkuse as main transcript	c.17A>G	p.Lys6Arg	missense_variant	2/16	ENST00000649286.2
AGK	NM_001364948.3 linkuse as main transcript	c.17A>G	p.Lys6Arg	missense_variant	2/15
AGK	XM_011516397.4 linkuse as main transcript	c.17A>G	p.Lys6Arg	missense_variant	2/16
AGK	XM_024446835.2 linkuse as main transcript	c.17A>G	p.Lys6Arg	missense_variant	2/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AGK	ENST00000649286.2 linkuse as main transcript	c.17A>G	p.Lys6Arg	missense_variant	2/16		NM_018238.4	P1	Q53H12-1

Frequencies

GnomAD3 genomes

AF:

0.00221

AC:

337

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00550

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00157

Gnomad ASJ

AF:

0.0141

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000382

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.00151

AC:

379

AN:

251240

Hom.:

AF XY:

0.00132

AC XY:

179

AN XY:

135782

show subpopulations

Gnomad AFR exome

AF:

0.00499

Gnomad AMR exome

AF:

0.00110

Gnomad ASJ exome

AF:

0.0180

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000528

Gnomad OTH exome

AF:

0.00310

GnomAD4 exome

AF:

0.000789

AC:

1153

AN:

1461698

Hom.:

Cov.:

AF XY:

0.000794

AC XY:

577

AN XY:

727140

show subpopulations

Gnomad4 AFR exome

AF:

0.00484

Gnomad4 AMR exome

AF:

0.00136

Gnomad4 ASJ exome

AF:

0.0170

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.0000562

Gnomad4 NFE exome

AF:

0.000280

Gnomad4 OTH exome

AF:

0.00268

GnomAD4 genome

AF:

0.00222

AC:

338

AN:

152328

Hom.:

Cov.:

AF XY:

0.00191

AC XY:

142

AN XY:

74504

show subpopulations

Gnomad4 AFR

AF:

0.00551

Gnomad4 AMR

AF:

0.00157

Gnomad4 ASJ

AF:

0.0141

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000382

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.00164

Hom.:

Bravo

AF:

0.00278

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00454

AC:

ESP6500EA

AF:

0.00163

AC:

ExAC

AF:

0.00146

AC:

177

EpiCase

AF:

0.000927

EpiControl

AF:

0.000889

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Mar 01, 2022	AGK: BS1, BS2 -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 08, 2019	- -

Sengers syndrome

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

Sengers syndrome;C3553494:Cataract 38

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 25, 2024

- -

Cataract 38

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.43

Cadd

Benign

Dann

Uncertain

0.99

DEOGEN2

Benign

0.024

T;T;T;T;T;.;.

Eigen

Benign

-0.34

Eigen_PC

Benign

-0.18

FATHMM_MKL

Benign

0.66

MetaRNN

Benign

0.0059

T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.90

L;.;L;L;L;.;L

MutationTaster

Benign

0.96

D;D;D;N

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-0.45

N;.;.;.;.;.;N

REVEL

Benign

0.038

Sift

Benign

0.52

T;.;.;.;.;.;T

Sift4G

Benign

0.88

T;T;.;.;.;.;T

Polyphen

0.019

B;.;B;B;B;.;.

Vest4

0.091

MVP

0.61

MPC

0.16

ClinPred

0.0046

GERP RS

2.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.033

gMVP

0.59

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