3-38518854-A-G

Variant names:

• chr3-38518854-A-G
• rs2051215
• NM_005107.4:c.646-5047A>G

Variant summary

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

The NM_005107.4(EXOG):​c.646-5047A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.573 in 152,046 control chromosomes in the GnomAD database, including 27,333 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 0.57 (27333 hom., cov: 32)
• Consequence: EXOG NM_005107.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.221
• Publications: 9 publications found

Genes affected

EXOG (HGNC:3347): (exo/endonuclease G) This gene encodes an endo/exonuclease with 5'-3' exonuclease activity. The encoded enzyme catalyzes the hydrolysis of ester linkages at the 5' end of a nucleic acid chain. This enzyme is localized to the mitochondria and may play a role in programmed cell death. Alternatively spliced transcript variants have been described. A pseudogene exists on chromosome 18. [provided by RefSeq, Feb 2009]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.814 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EXOG	NM_005107.4	c.646-5047A>G		intron_variant	Intron 5 of 5	ENST00000287675.10	NP_005098.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EXOG	ENST00000287675.10	c.646-5047A>G		intron_variant	Intron 5 of 5	1	NM_005107.4	ENSP00000287675.5

Frequencies

GnomAD3 genomes AF: 0.573 AC: 87035 AN: 151928 Hom.: 27279 Cov.: 32

Gnomad AFR AF: 0.821

Gnomad AMI AF: 0.535

Gnomad AMR AF: 0.612

Gnomad ASJ AF: 0.508

Gnomad EAS AF: 0.740

Gnomad SAS AF: 0.491

Gnomad FIN AF: 0.465

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.428

Gnomad OTH AF: 0.552

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

GnomAD4 genome AF: 0.573 AC: 87152 AN: 152046 Hom.: 27333 Cov.: 32 AF XY: 0.576 AC XY: 42786 AN XY: 74318

African (AFR) AF: 0.821 AC: 34082 AN: 41488

American (AMR) AF: 0.612 AC: 9354 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.508 AC: 1757 AN: 3462

East Asian (EAS) AF: 0.740 AC: 3825 AN: 5168

South Asian (SAS) AF: 0.491 AC: 2363 AN: 4812

European-Finnish (FIN) AF: 0.465 AC: 4915 AN: 10566

Middle Eastern (MID) AF: 0.520 AC: 153 AN: 294

European-Non Finnish (NFE) AF: 0.428 AC: 29053 AN: 67956

Other (OTH) AF: 0.552 AC: 1162 AN: 2104

Alfa AF: 0.498 Hom.: 5031

Bravo AF: 0.600

Asia WGS AF: 0.604 AC: 2100 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.75
DANN	Benign	0.56
PhyloP100		-0.22
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: rs2051215; hg19: chr3-38560345;