rs1567126045

Variant names:

• chr16-85401-G-A
• NM_001015052.3:c.506G>A

Your query was ambiguous. Multiple possible variants found:

• chr16-85401-G-A
• chr16-85401-G-C
• chr16-85401-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001015052.3(MPG):​c.506G>A​(p.Gly169Glu) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000069 in 1,448,564 control chromosomes in the GnomAD database, with no homozygous occurrence. 2/3 splice prediction tools predicting alterations to normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: MPG NM_001015052.3 missense, splice_region
• Scores: Splicing: ADA: 0.9979
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.87

Genes affected

MPG (HGNC:7211): (N-methylpurine DNA glycosylase) Predicted to enable alkylbase DNA N-glycosylase activity. Predicted to be involved in base-excision repair. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

NPRL3 (HGNC:14124): (NPR3 like, GATOR1 complex subunit) Contributes to GTPase activator activity. Involved in cellular response to amino acid starvation and negative regulation of TOR signaling. Located in lysosomal membrane. Part of GATOR1 complex. Implicated in focal epilepsy. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MPG	NM_001015052.3	c.506G>A	p.Gly169Glu	missense_variant, splice_region_variant	Exon 4 of 4	ENST00000356432.8	NP_001015052.1
NPRL3	NM_001077350.3	c.*1304C>T		3_prime_UTR_variant	Exon 14 of 14	ENST00000611875.5	NP_001070818.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MPG	ENST00000356432.8	c.506G>A	p.Gly169Glu	missense_variant, splice_region_variant	Exon 4 of 4	1	NM_001015052.3	ENSP00000348809.4
NPRL3	ENST00000611875	c.*1304C>T		3_prime_UTR_variant	Exon 14 of 14	5	NM_001077350.3	ENSP00000478273.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 6.90e-7 AC: 1 AN: 1448564 Hom.: 0 Cov.: 31 AF XY: 0.00000139 AC XY: 1 AN XY: 719172

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: 9.05e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Uncertain	0.051	T
BayesDel_noAF	Benign	-0.16
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Benign	0.081	T;.;.;T
Eigen	Uncertain	0.67
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.96	D;D;D;D
M_CAP	Benign	0.050	D
MetaRNN	Uncertain	0.68	D;D;D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	.;.;.;L
PrimateAI	Uncertain	0.68	T
PROVEAN	Pathogenic	-4.9	D;D;D;D
REVEL	Benign	0.24
Sift	Benign	0.23	T;T;T;T
Sift4G	Benign	0.36	T;T;T;T
Polyphen		0.99	.;.;.;D
Vest4		0.49, 0.48, 0.48
MutPred		0.48		.;.;.;Loss of catalytic residue at G174 (P = 0.0078);
MVP		0.80
MPC		0.38
ClinPred		0.99	D
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.60
gMVP		0.85

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	1.0
dbscSNV1_RF	Pathogenic	0.89
SpliceAI score (max)		0.060		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: chr16-135400;