chr3-38523956-C-T

Variant names:

• chr3-38523956-C-T
• rs755253280
• NM_005107.4:c.701C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005107.4(EXOG):​c.701C>T​(p.Ala234Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000207 in 1,452,302 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: EXOG NM_005107.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.40
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23623219).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005107.4. 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
	EXOG	NM_005107.4	MANE Select	c.701C>T	p.Ala234Val	missense	Exon 6 of 6	NP_005098.2	Q9Y2C4-1
	EXOG	NM_001145464.2		c.551C>T	p.Ala184Val	missense	Exon 5 of 5	NP_001138936.1	Q9Y2C4-4
	EXOG	NR_134938.2		n.754C>T		non_coding_transcript_exon	Exon 7 of 8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EXOG	ENST00000287675.10	TSL:1 MANE Select	c.701C>T	p.Ala234Val	missense	Exon 6 of 6	ENSP00000287675.5	Q9Y2C4-1
	EXOG	ENST00000412107.5	TSL:1	n.*598C>T		non_coding_transcript_exon	Exon 8 of 8	ENSP00000400239.1	F2Z2D3
	EXOG	ENST00000431472.5	TSL:1	n.*444C>T		non_coding_transcript_exon	Exon 7 of 7	ENSP00000394977.1	F8WE28

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000814 AC: 2 AN: 245608 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000604

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000207 AC: 3 AN: 1452302 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 721438

African (AFR) AF: 0.00 AC: 0 AN: 32992

American (AMR) AF: 0.0000696 AC: 3 AN: 43092

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25712

East Asian (EAS) AF: 0.00 AC: 0 AN: 39548

South Asian (SAS) AF: 0.00 AC: 0 AN: 84996

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53282

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5712

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1107102

Other (OTH) AF: 0.00 AC: 0 AN: 59866

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T
Eigen	Uncertain	0.28
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.0068	T
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-1.2	T
MutationAssessor	Benign	0.96	L
PhyloP100		2.4
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.15
Sift	Benign	0.34	T
Sift4G	Benign	0.39	T
Polyphen		0.90	P
Vest4		0.21
MutPred		0.65		Loss of disorder (P = 0.1128)
MVP		0.20
MPC		0.38
ClinPred		0.51	D
GERP RS		5.5
Varity_R		0.21
gMVP		0.62
Mutation Taster		=60/40	polymorphism

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: rs755253280; hg19: chr3-38565447;