7-141551465-C-G

Position:

• chr7-141551465-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.180

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AGK	NM_018238.4	c.-15+31C>G		intron_variant		ENST00000649286.2	NP_060708.1
AGK	XM_024446835.2	c.-168C>G		5_prime_UTR_variant	1/16		XP_024302603.1
AGK	NM_001364948.3	c.-15+31C>G		intron_variant			NP_001351877.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AGK	ENST00000649286.2	c.-15+31C>G		intron_variant			NM_018238.4	ENSP00000497280	P1

Frequencies

GnomAD3 genomes AF: 0.0913 AC: 13896 AN: 152166 Hom.: 1389 Cov.: 33

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: 37 AN: 970 Hom.: 1 Cov.: 0 AF XY: 0.0372 AC XY: 27 AN XY: 726

Gnomad4 AFR exome AF: 0.167

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.100

Gnomad4 SAS exome AF: 0.0909

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0303

Gnomad4 OTH exome AF: 0.105

GnomAD4 genome AF: 0.0916 AC: 13955 AN: 152276 Hom.: 1399 Cov.: 33 AF XY: 0.0908 AC XY: 6758 AN XY: 74468

Gnomad4 AFR AF: 0.247

Gnomad4 AMR AF: 0.0435

Gnomad4 ASJ AF: 0.0187

Gnomad4 EAS AF: 0.0379

Gnomad4 SAS AF: 0.150

Gnomad4 FIN AF: 0.0127

Gnomad4 NFE AF: 0.0258

Gnomad4 OTH AF: 0.0723

Alfa AF: 0.0625 Hom.: 95

Bravo AF: 0.100

Asia WGS AF: 0.109 AC: 377 AN: 3470

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 21, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.8
DANN	Benign	0.34
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Other links and lift over

dbSNP: rs13242345; hg19: chr7-141251265;