16-79493-C-T

Variant names:

• chr16-79493-C-T
• rs2266605
• NM_001015052.3:c.93C>T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_001015052.3(MPG):​c.93C>T​(p.Asp31Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00108 in 1,612,700 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0054 (10 hom., cov: 33)
  • Exomes 𝑓: 0.00063 (12 hom.)
• Consequence: MPG NM_001015052.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.171
• Publications: 5 publications found

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]

MPG Gene-Disease associations (from GenCC):

• schizophrenia

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant 16-79493-C-T is Benign according to our data. Variant chr16-79493-C-T is described in ClinVar as Benign. ClinVar VariationId is 787967.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.171 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00539 (820/152126) while in subpopulation AFR AF = 0.0184 (765/41496). AF 95% confidence interval is 0.0174. There are 10 homozygotes in GnomAd4. There are 417 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 10 Unknown gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001015052.3. 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
	MPG	NM_001015052.3	MANE Select	c.93C>T	p.Asp31Asp	synonymous	Exon 2 of 4	NP_001015052.1	P29372-4
	MPG	NM_002434.4		c.108C>T	p.Asp36Asp	synonymous	Exon 3 of 5	NP_002425.2	Q1W6H1
	MPG	NM_001015054.3		c.57C>T	p.Asp19Asp	synonymous	Exon 2 of 4	NP_001015054.1	P29372-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MPG	ENST00000356432.8	TSL:1 MANE Select	c.93C>T	p.Asp31Asp	synonymous	Exon 2 of 4	ENSP00000348809.4	P29372-4
	MPG	ENST00000219431.4	TSL:3	c.108C>T	p.Asp36Asp	synonymous	Exon 3 of 5	ENSP00000219431.4	P29372-1
	MPG	ENST00000397817.5	TSL:2	c.57C>T	p.Asp19Asp	synonymous	Exon 2 of 4	ENSP00000380918.1	P29372-5

Frequencies

GnomAD3 genomes AF: 0.00539 AC: 819 AN: 152008 Hom.: 10 Cov.: 33

Gnomad AFR AF: 0.0185

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00256

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00336

GnomAD2 exomes AF: 0.00165 AC: 412 AN: 249896 AF XY: 0.00131

Gnomad AFR exome AF: 0.0198

Gnomad AMR exome AF: 0.000810

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000356

Gnomad OTH exome AF: 0.000327

GnomAD4 exome AF: 0.000633 AC: 924 AN: 1460574 Hom.: 12 Cov.: 32 AF XY: 0.000606 AC XY: 440 AN XY: 726610

African (AFR) AF: 0.0188 AC: 629 AN: 33470

American (AMR) AF: 0.00101 AC: 45 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00183 AC: 158 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52364

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5768

European-Non Finnish (NFE) AF: 0.0000162 AC: 18 AN: 1111806

Other (OTH) AF: 0.00119 AC: 72 AN: 60362

GnomAD4 genome AF: 0.00539 AC: 820 AN: 152126 Hom.: 10 Cov.: 33 AF XY: 0.00561 AC XY: 417 AN XY: 74350

African (AFR) AF: 0.0184 AC: 765 AN: 41496

American (AMR) AF: 0.00255 AC: 39 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00145 AC: 7 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10592

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 67990

Other (OTH) AF: 0.00332 AC: 7 AN: 2108

Alfa AF: 0.00215 Hom.: 2

Bravo AF: 0.00643

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	7.6
DANN	Benign	0.64
PhyloP100		-0.17
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	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: rs2266605; hg19: chr16-129492;