16-79278-A-G

Position:

• chr16-79278-A-G

Variant summary

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

The NM_001015052.3(MPG):​c.25-147A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0626 in 1,569,880 control chromosomes in the GnomAD database, including 19,906 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 0.21 (9378 hom., cov: 33)
  • Exomes 𝑓: 0.046 (10528 hom.)
• Consequence: MPG NM_001015052.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.42

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.648 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MPG	NM_001015052.3	c.25-147A>G		intron_variant		ENST00000356432.8	NP_001015052.1
MPG	NM_002434.4	c.-15A>G		5_prime_UTR_variant	2/5		NP_002425.2
MPG	NM_001015054.3	c.-12-147A>G		intron_variant			NP_001015054.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MPG	ENST00000356432.8	c.25-147A>G		intron_variant		1	NM_001015052.3	ENSP00000348809	P2

Frequencies

GnomAD3 genomes AF: 0.214 AC: 32491 AN: 152146 Hom.: 9330 Cov.: 33

Gnomad AFR AF: 0.654

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.148

Gnomad ASJ AF: 0.00893

Gnomad EAS AF: 0.112

Gnomad SAS AF: 0.183

Gnomad FIN AF: 0.0439

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.0118

Gnomad OTH AF: 0.171

GnomAD3 exomes AF: 0.107 AC: 19497 AN: 182872 Hom.: 3419 AF XY: 0.0965 AC XY: 9470 AN XY: 98132

Gnomad AFR exome AF: 0.675

Gnomad AMR exome AF: 0.163

Gnomad ASJ exome AF: 0.00880

Gnomad EAS exome AF: 0.113

Gnomad SAS exome AF: 0.169

Gnomad FIN exome AF: 0.0341

Gnomad NFE exome AF: 0.0119

Gnomad OTH exome AF: 0.0663

GnomAD4 exome AF: 0.0464 AC: 65741 AN: 1417616 Hom.: 10528 Cov.: 32 AF XY: 0.0474 AC XY: 33230 AN XY: 701638

Gnomad4 AFR exome AF: 0.690

Gnomad4 AMR exome AF: 0.164

Gnomad4 ASJ exome AF: 0.00757

Gnomad4 EAS exome AF: 0.129

Gnomad4 SAS exome AF: 0.165

Gnomad4 FIN exome AF: 0.0320

Gnomad4 NFE exome AF: 0.0111

Gnomad4 OTH exome AF: 0.0788

GnomAD4 genome AF: 0.214 AC: 32609 AN: 152264 Hom.: 9378 Cov.: 33 AF XY: 0.213 AC XY: 15897 AN XY: 74488

Gnomad4 AFR AF: 0.654

Gnomad4 AMR AF: 0.149

Gnomad4 ASJ AF: 0.00893

Gnomad4 EAS AF: 0.112

Gnomad4 SAS AF: 0.183

Gnomad4 FIN AF: 0.0439

Gnomad4 NFE AF: 0.0118

Gnomad4 OTH AF: 0.176

Alfa AF: 0.0832 Hom.: 2130

Bravo AF: 0.240

Asia WGS AF: 0.214 AC: 742 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.17
DANN	Benign	0.34

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: rs710080; hg19: chr16-129277; COSMIC: COSV54738355; COSMIC: COSV54738355;