Variant chr7-141601206-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_018238.4(AGK):c.223A>G(p.Lys75Glu) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000755 in 1,457,326 control chromosomes in the GnomAD database, with no homozygous occurrence. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

AGK
NM_018238.4 missense, splice_region

Scores

Splicing: ADA: 0.8634

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.49

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
AGK	NM_018238.4 linkuse as main transcript	c.223A>G	p.Lys75Glu	missense_variant, splice_region_variant	5/16	ENST00000649286.2
AGK	NM_001364948.3 linkuse as main transcript	c.223A>G	p.Lys75Glu	missense_variant, splice_region_variant	5/15
AGK	XM_011516397.4 linkuse as main transcript	c.223A>G	p.Lys75Glu	missense_variant, splice_region_variant	5/16
AGK	XM_024446835.2 linkuse as main transcript	c.223A>G	p.Lys75Glu	missense_variant, splice_region_variant	5/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AGK	ENST00000649286.2 linkuse as main transcript	c.223A>G	p.Lys75Glu	missense_variant, splice_region_variant	5/16		NM_018238.4	P1	Q53H12-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000755

AC:

AN:

1457326

Hom.:

Cov.:

AF XY:

0.00000828

AC XY:

AN XY:

725022

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.00000811

Gnomad4 OTH exome

AF:

0.0000332

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

AGK-related disorder

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genomic Research Center, Shahid Beheshti University of Medical Sciences

Dec 18, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.34

BayesDel_addAF

Uncertain

0.034

BayesDel_noAF

Benign

-0.19

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.20

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

Eigen

Uncertain

0.54

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.93

.;D;.;D;.;D;D

M_CAP

Benign

0.018

MetaRNN

Uncertain

0.54

D;D;D;D;D;D;D

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

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

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.71

PROVEAN

Uncertain

-2.5

D;D;.;.;.;.;.

REVEL

Benign

0.18

Sift

Benign

0.12

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

Sift4G

Benign

0.14

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

Polyphen

0.90

P;.;P;.;P;P;.

Vest4

0.80

MutPred

0.58

Loss of MoRF binding (P = 0.0265);.;Loss of MoRF binding (P = 0.0265);.;Loss of MoRF binding (P = 0.0265);Loss of MoRF binding (P = 0.0265);Loss of MoRF binding (P = 0.0265);

MVP

0.28

MPC

0.89

ClinPred

0.96

GERP RS

5.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.79

gMVP

0.75

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.86

dbscSNV1_RF

Benign

0.69

SpliceAI score (max)

0.040

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