ENST00000567503.1:n.61G>C

Variant names:

• chr7-141551244-C-G
• rs7795885
• ENST00000567503.1:n.61G>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000567503.1(AGK-DT):​n.61G>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0925 in 152,302 control chromosomes in the GnomAD database, including 1,420 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.092 (1420 hom., cov: 32)
  • Exomes 𝑓: 0.043 (0 hom.)
• Consequence: AGK-DT ENST00000567503.1 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.19
• Publications: 2 publications found

Genes affected

AGK-DT (HGNC:55356): (AGK divergent transcript)

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: Orphanet, Labcorp Genetics (formerly Invitae), G2P
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 7-141551244-C-G is Benign according to our data. Variant chr7-141551244-C-G is described in ClinVar as Benign. ClinVar VariationId is 1329639.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.245 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000567503.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGK-DT	NR_183402.1		n.101G>C		non_coding_transcript_exon	Exon 1 of 4
	AGK-DT	NR_183403.1		n.101G>C		non_coding_transcript_exon	Exon 1 of 3
	AGK-DT	NR_183404.1		n.101G>C		non_coding_transcript_exon	Exon 1 of 5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGK-DT	ENST00000567503.1	TSL:3	n.61G>C		non_coding_transcript_exon	Exon 1 of 4
	AGK-DT	ENST00000666392.2		n.67G>C		non_coding_transcript_exon	Exon 1 of 3
	AGK-DT	ENST00000668372.1		n.29G>C		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes AF: 0.0921 AC: 14019 AN: 152140 Hom.: 1410 Cov.: 32

Gnomad AFR AF: 0.249

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0442

Gnomad ASJ AF: 0.0190

Gnomad EAS AF: 0.0385

Gnomad SAS AF: 0.149

Gnomad FIN AF: 0.0127

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0258

Gnomad OTH AF: 0.0740

GnomAD4 exome AF: 0.0435 AC: 2 AN: 46 Hom.: 0 Cov.: 0 AF XY: 0.0250 AC XY: 1 AN XY: 40

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.500 AC: 1 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.0263 AC: 1 AN: 38

Other (OTH) AF: 0.00 AC: 0 AN: 4

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0385499), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0925 AC: 14080 AN: 152256 Hom.: 1420 Cov.: 32 AF XY: 0.0915 AC XY: 6809 AN XY: 74444

African (AFR) AF: 0.249 AC: 10354 AN: 41514

American (AMR) AF: 0.0444 AC: 680 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0190 AC: 66 AN: 3470

East Asian (EAS) AF: 0.0386 AC: 200 AN: 5180

South Asian (SAS) AF: 0.150 AC: 725 AN: 4828

European-Finnish (FIN) AF: 0.0127 AC: 135 AN: 10622

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0258 AC: 1752 AN: 68016

Other (OTH) AF: 0.0742 AC: 157 AN: 2116

Alfa AF: 0.0626 Hom.: 95

Bravo AF: 0.100

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.2
DANN	Benign	0.56
PhyloP100		-3.2
PromoterAI		-0.041	Neutral
Mutation Taster		=300/0	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: rs7795885; hg19: chr7-141251044;