3-38518258-A-G

Position:

• chr3-38518258-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005107.4(EXOG):​c.646-5643A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.231 in 152,116 control chromosomes in the GnomAD database, including 4,134 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 0.23 (4134 hom., cov: 32)
• Consequence: EXOG NM_005107.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.08

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.303 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EXOG	NM_005107.4	c.646-5643A>G		intron_variant		ENST00000287675.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EXOG	ENST00000287675.10	c.646-5643A>G		intron_variant		1	NM_005107.4	P1

Frequencies

GnomAD3 genomes AF: 0.231 AC: 35127 AN: 151998 Hom.: 4139 Cov.: 32

Gnomad AFR AF: 0.176

Gnomad AMI AF: 0.297

Gnomad AMR AF: 0.232

Gnomad ASJ AF: 0.271

Gnomad EAS AF: 0.316

Gnomad SAS AF: 0.241

Gnomad FIN AF: 0.277

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.247

Gnomad OTH AF: 0.233

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

GnomAD4 genome AF: 0.231 AC: 35131 AN: 152116 Hom.: 4134 Cov.: 32 AF XY: 0.233 AC XY: 17355 AN XY: 74382

Gnomad4 AFR AF: 0.176

Gnomad4 AMR AF: 0.232

Gnomad4 ASJ AF: 0.271

Gnomad4 EAS AF: 0.316

Gnomad4 SAS AF: 0.242

Gnomad4 FIN AF: 0.277

Gnomad4 NFE AF: 0.247

Gnomad4 OTH AF: 0.233

Alfa AF: 0.248 Hom.: 8912

Bravo AF: 0.228

Asia WGS AF: 0.264 AC: 920 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	12
DANN	Benign	0.75

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: rs2051211; hg19: chr3-38559749;