NM_001346953.2:c.515G>A

Variant names:

• chr1-40515059-G-A
• NM_001346953.2:c.515G>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001346953.2(EXO5):​c.515G>A​(p.Gly172Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,860 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G172V) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: EXO5 NM_001346953.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.14

Genes affected

EXO5 (HGNC:26115): (exonuclease 5) The protein encoded by this gene is a single-stranded DNA (ssDNA)-specific exonuclease that can slide along the DNA before cutting it. However, human replication protein A binds ssDNA and restricts sliding of the encoded protein, providing a 5'-directionality to the enzyme. This protein localizes to nuclear repair loci after DNA damage. [provided by RefSeq, Nov 2016]

ENSG00000227278 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.060515106).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EXO5	NM_001346953.2	c.515G>A	p.Gly172Glu	missense_variant	Exon 4 of 4	ENST00000415550.6	NP_001333882.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EXO5	ENST00000415550.6	c.515G>A	p.Gly172Glu	missense_variant	Exon 4 of 4	2	NM_001346953.2	ENSP00000413565.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461860 Hom.: 0 Cov.: 49 AF XY: 0.00000138 AC XY: 1 AN XY: 727230

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	22
DANN	Benign	0.95
DEOGEN2	Benign	0.0014	T;T;.;T;.;.;.
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.33
FATHMM_MKL	Benign	0.55	D
LIST_S2	Benign	0.43	.;.;T;T;T;.;T
M_CAP	Benign	0.0033	T
MetaRNN	Benign	0.061	T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.34	N;N;.;N;.;.;.
PrimateAI	Benign	0.41	T
PROVEAN	Benign	0.74	N;N;N;N;N;N;N
REVEL	Benign	0.12
Sift	Benign	0.83	T;T;T;T;T;T;T
Sift4G	Benign	0.42	T;T;T;T;T;T;T
Polyphen		0.0020	B;B;.;B;.;.;.
Vest4		0.18
MutPred		0.47		Gain of sheet (P = 0.0101);Gain of sheet (P = 0.0101);Gain of sheet (P = 0.0101);Gain of sheet (P = 0.0101);Gain of sheet (P = 0.0101);Gain of sheet (P = 0.0101);Gain of sheet (P = 0.0101);
MVP		0.10
MPC		0.19
ClinPred		0.071	T
GERP RS		4.0
Varity_R		0.091
gMVP		0.60

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-40980731;