3-38497621-A-T

Position:

• chr3-38497621-A-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_005107.4(EXOG):​c.164-8A>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.035 (0 hom., cov: 21)
  • Exomes 𝑓: 0.016 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: EXOG NM_005107.4 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.000009529
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.75

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 Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 3-38497621-A-T is Benign according to our data. Variant chr3-38497621-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 788221.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EXOG	NM_005107.4	c.164-8A>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000287675.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EXOG	ENST00000287675.10	c.164-8A>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_005107.4	P1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 2395 AN: 68656 Hom.: 0 Cov.: 21 FAILED QC

Gnomad AFR AF: 0.0220

Gnomad AMI AF: 0.0399

Gnomad AMR AF: 0.0198

Gnomad ASJ AF: 0.0322

Gnomad EAS AF: 0.0155

Gnomad SAS AF: 0.0296

Gnomad FIN AF: 0.0265

Gnomad MID AF: 0.0308

Gnomad NFE AF: 0.0485

Gnomad OTH AF: 0.0272

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0161 AC: 17754 AN: 1104088 Hom.: 0 Cov.: 33 AF XY: 0.0187 AC XY: 10022 AN XY: 535192

Gnomad4 AFR exome AF: 0.00574

Gnomad4 AMR exome AF: 0.0420

Gnomad4 ASJ exome AF: 0.0334

Gnomad4 EAS exome AF: 0.0134

Gnomad4 SAS exome AF: 0.0902

Gnomad4 FIN exome AF: 0.0838

Gnomad4 NFE exome AF: 0.0106

Gnomad4 OTH exome AF: 0.0165

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0349 AC: 2396 AN: 68668 Hom.: 0 Cov.: 21 AF XY: 0.0313 AC XY: 1042 AN XY: 33326

Gnomad4 AFR AF: 0.0220

Gnomad4 AMR AF: 0.0198

Gnomad4 ASJ AF: 0.0322

Gnomad4 EAS AF: 0.0156

Gnomad4 SAS AF: 0.0298

Gnomad4 FIN AF: 0.0265

Gnomad4 NFE AF: 0.0486

Gnomad4 OTH AF: 0.0272

Alfa AF: 0.000521 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.11
DANN	Benign	0.35

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0000095
dbscSNV1_RF	Benign	0.0
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: rs201455368; hg19: chr3-38539112;