7-141551287-G-A

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Strong BS1_Supporting BS2

The NR_183408.1(AGK-DT):n.58C>T 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 0.000906 in 152,308 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00091 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: AGK-DT NR_183408.1 non_coding_transcript_exon
• Clinical Significance: Uncertain significance criteria provided, single submitter U:2
• Conservation: PhyloP100: 1.15

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]

ACMG classification

Verdict is Benign. Variant got -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000906 (138/152308) while in subpopulation EAS AF= 0.0199 (103/5174). AF 95% confidence interval is 0.0168. There are 3 homozygotes in gnomad4. There are 72 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
• BS2: High Homozygotes in GnomAd at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AGK-DT	NR_183408.1	n.58C>T		non_coding_transcript_exon_variant	1/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AGK	ENST00000629555.2	c.-162G>A		5_prime_UTR_variant	1/15	5
AGK-DT	ENST00000567503.1	n.18C>T		non_coding_transcript_exon_variant	1/4	3
AGK-DT	ENST00000668372.1			upstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.000913 AC: 139 AN: 152194 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000916

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0198

Gnomad SAS AF: 0.000828

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00239

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 40 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 36

Gnomad4 AMR exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.000906 AC: 138 AN: 152308 Hom.: 3 Cov.: 32 AF XY: 0.000967 AC XY: 72 AN XY: 74482

Gnomad4 AFR AF: 0.000168

Gnomad4 AMR AF: 0.000914

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0199

Gnomad4 SAS AF: 0.000829

Gnomad4 FIN AF: 0.0000941

Gnomad4 NFE AF: 0.0000735

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.000347 Hom.: 0

Bravo AF: 0.00110

Asia WGS AF: 0.00953 AC: 33 AN: 3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, single submitter

Submissions by phenotype

Sengers syndrome Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Developmental cataract Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	8.0
Dann	Benign	0.91

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: rs148553992; hg19: chr7-141251087;