rs4725559

Variant names:

• chr7-141587852-G-A
• rs4725559
• NM_018238.4:c.102-5294G>A

Variant summary

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

The NM_018238.4(AGK):​c.102-5294G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.366 in 152,006 control chromosomes in the GnomAD database, including 11,285 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 0.37 (11285 hom., cov: 32)
• Consequence: AGK NM_018238.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.254
• Publications: 8 publications found

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 Gene-Disease associations (from GenCC):

• mitochondrial disease

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• Sengers syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet
• total early-onset cataract

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• cataract 38

  Inheritance: AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.522 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGK	NM_018238.4	c.102-5294G>A		intron_variant	Intron 2 of 15	ENST00000649286.2	NP_060708.1
AGK	NM_001364948.3	c.102-5294G>A		intron_variant	Intron 2 of 14		NP_001351877.1
AGK	XM_011516397.4	c.102-5294G>A		intron_variant	Intron 2 of 15		XP_011514699.1
AGK	XM_024446835.2	c.102-5294G>A		intron_variant	Intron 2 of 15		XP_024302603.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGK	ENST00000649286.2	c.102-5294G>A		intron_variant	Intron 2 of 15		NM_018238.4	ENSP00000497280.1

Frequencies

GnomAD3 genomes AF: 0.366 AC: 55546 AN: 151888 Hom.: 11276 Cov.: 32

Gnomad AFR AF: 0.175

Gnomad AMI AF: 0.398

Gnomad AMR AF: 0.482

Gnomad ASJ AF: 0.390

Gnomad EAS AF: 0.539

Gnomad SAS AF: 0.367

Gnomad FIN AF: 0.447

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.427

Gnomad OTH AF: 0.402

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

GnomAD4 genome AF: 0.366 AC: 55567 AN: 152006 Hom.: 11285 Cov.: 32 AF XY: 0.370 AC XY: 27451 AN XY: 74266

African (AFR) AF: 0.174 AC: 7230 AN: 41490

American (AMR) AF: 0.482 AC: 7366 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.390 AC: 1354 AN: 3470

East Asian (EAS) AF: 0.539 AC: 2788 AN: 5174

South Asian (SAS) AF: 0.367 AC: 1765 AN: 4810

European-Finnish (FIN) AF: 0.447 AC: 4713 AN: 10532

Middle Eastern (MID) AF: 0.361 AC: 106 AN: 294

European-Non Finnish (NFE) AF: 0.427 AC: 29022 AN: 67946

Other (OTH) AF: 0.409 AC: 861 AN: 2106

Alfa AF: 0.416 Hom.: 17443

Bravo AF: 0.363

Asia WGS AF: 0.431 AC: 1499 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.20
DANN	Benign	0.51
PhyloP100		-0.25
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: rs4725559; hg19: chr7-141287652;