chr7-141555184-A-G

Position:

• chr7-141555184-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_018238.4(AGK):​c.-14-269A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0353 in 152,246 control chromosomes in the GnomAD database, including 145 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.035 (145 hom., cov: 32)
• Consequence: AGK NM_018238.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.126

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 7-141555184-A-G is Benign according to our data. Variant chr7-141555184-A-G is described in ClinVar as [Benign]. Clinvar id is 669749.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.139 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AGK	NM_018238.4	c.-14-269A>G		intron_variant		ENST00000649286.2	NP_060708.1
AGK	XM_011516397.4	c.-148A>G		5_prime_UTR_variant	1/16		XP_011514699.1
AGK	NM_001364948.3	c.-14-269A>G		intron_variant			NP_001351877.1
AGK	XM_024446835.2	c.-14-269A>G		intron_variant			XP_024302603.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AGK	ENST00000649286.2	c.-14-269A>G		intron_variant			NM_018238.4	ENSP00000497280	P1

Frequencies

GnomAD3 genomes AF: 0.0352 AC: 5360 AN: 152128 Hom.: 143 Cov.: 32

Gnomad AFR AF: 0.0527

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0253

Gnomad ASJ AF: 0.00490

Gnomad EAS AF: 0.0360

Gnomad SAS AF: 0.147

Gnomad FIN AF: 0.0126

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0246

Gnomad OTH AF: 0.0291

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

GnomAD4 genome AF: 0.0353 AC: 5381 AN: 152246 Hom.: 145 Cov.: 32 AF XY: 0.0371 AC XY: 2758 AN XY: 74430

Gnomad4 AFR AF: 0.0529

Gnomad4 AMR AF: 0.0256

Gnomad4 ASJ AF: 0.00490

Gnomad4 EAS AF: 0.0361

Gnomad4 SAS AF: 0.148

Gnomad4 FIN AF: 0.0126

Gnomad4 NFE AF: 0.0246

Gnomad4 OTH AF: 0.0298

Alfa AF: 0.0256 Hom.: 63

Bravo AF: 0.0346

Asia WGS AF: 0.0960 AC: 332 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.7
DANN	Benign	0.81

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: rs12669650; hg19: chr7-141254984;