rs11773340

Variant names:

• chr7-141617034-C-T
• rs11773340
• NM_018238.4:c.518+1469C>T

Variant summary

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

The NM_018238.4(AGK):​c.518+1469C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.377 in 151,872 control chromosomes in the GnomAD database, including 11,717 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 0.38 (11717 hom., cov: 31)
• Consequence: AGK NM_018238.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.394
• Publications: 7 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.524 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGK	NM_018238.4	c.518+1469C>T		intron_variant	Intron 8 of 15	ENST00000649286.2	NP_060708.1
AGK	NM_001364948.3	c.518+1469C>T		intron_variant	Intron 8 of 14		NP_001351877.1
AGK	XM_011516397.4	c.518+1469C>T		intron_variant	Intron 8 of 15		XP_011514699.1
AGK	XM_024446835.2	c.518+1469C>T		intron_variant	Intron 8 of 15		XP_024302603.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGK	ENST00000649286.2	c.518+1469C>T		intron_variant	Intron 8 of 15		NM_018238.4	ENSP00000497280.1

Frequencies

GnomAD3 genomes AF: 0.377 AC: 57237 AN: 151752 Hom.: 11710 Cov.: 31

Gnomad AFR AF: 0.206

Gnomad AMI AF: 0.399

Gnomad AMR AF: 0.490

Gnomad ASJ AF: 0.390

Gnomad EAS AF: 0.540

Gnomad SAS AF: 0.369

Gnomad FIN AF: 0.447

Gnomad MID AF: 0.369

Gnomad NFE AF: 0.431

Gnomad OTH AF: 0.410

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

GnomAD4 genome AF: 0.377 AC: 57259 AN: 151872 Hom.: 11717 Cov.: 31 AF XY: 0.381 AC XY: 28238 AN XY: 74204

African (AFR) AF: 0.206 AC: 8521 AN: 41426

American (AMR) AF: 0.490 AC: 7474 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.390 AC: 1353 AN: 3466

East Asian (EAS) AF: 0.540 AC: 2780 AN: 5144

South Asian (SAS) AF: 0.370 AC: 1781 AN: 4814

European-Finnish (FIN) AF: 0.447 AC: 4711 AN: 10530

Middle Eastern (MID) AF: 0.373 AC: 109 AN: 292

European-Non Finnish (NFE) AF: 0.431 AC: 29288 AN: 67912

Other (OTH) AF: 0.416 AC: 878 AN: 2112

Alfa AF: 0.423 Hom.: 17956

Bravo AF: 0.377

Asia WGS AF: 0.434 AC: 1510 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.6
DANN	Benign	0.86
PhyloP100		-0.39
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: rs11773340; hg19: chr7-141316834;