chr16-79459-C-T

Variant names:

• chr16-79459-C-T
• NM_001015052.3:c.59C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001015052.3(MPG):​c.59C>T​(p.Pro20Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P20A) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: MPG NM_001015052.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.382
• Publications: 0 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: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.032319695).
• BP6: Variant 16-79459-C-T is Benign according to our data. Variant chr16-79459-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3201801.Status of the report is criteria_provided_single_submitter, 1 stars.

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.59C>T	p.Pro20Leu	missense	Exon 2 of 4	NP_001015052.1	P29372-4
	MPG	NM_002434.4		c.74C>T	p.Pro25Leu	missense	Exon 3 of 5	NP_002425.2	Q1W6H1
	MPG	NM_001015054.3		c.23C>T	p.Pro8Leu	missense	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.59C>T	p.Pro20Leu	missense	Exon 2 of 4	ENSP00000348809.4	P29372-4
	MPG	ENST00000219431.4	TSL:3	c.74C>T	p.Pro25Leu	missense	Exon 3 of 5	ENSP00000219431.4	P29372-1
	MPG	ENST00000397817.5	TSL:2	c.23C>T	p.Pro8Leu	missense	Exon 2 of 4	ENSP00000380918.1	P29372-5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Likely benign

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	0.072
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.098
DANN	Benign	0.82
DEOGEN2	Benign	0.0043	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0054	N
LIST_S2	Benign	0.50	T
M_CAP	Benign	0.0013	T
MetaRNN	Benign	0.032	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-1.5	N
PhyloP100		-0.38
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-0.14	N
REVEL	Benign	0.0060
Sift	Benign	0.31	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.10
MutPred		0.24		Gain of helix (P = 0.0128)
MVP		0.25
MPC		0.054
ClinPred		0.16	T
GERP RS		-1.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.014
gMVP		0.11

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

hg19: chr16-129458;