16-83239-T-C

Position:

• chr16-83239-T-C

Variant summary

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

The NM_001015052.3(MPG):​c.488T>C​(p.Met163Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MPG NM_001015052.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.93

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 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/exons	MANE	UniProt
MPG	NM_001015052.3	c.488T>C	p.Met163Thr	missense_variant	3/4	ENST00000356432.8
MPG	NM_002434.4	c.503T>C	p.Met168Thr	missense_variant	4/5
MPG	NM_001015054.3	c.452T>C	p.Met151Thr	missense_variant	3/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MPG	ENST00000356432.8	c.488T>C	p.Met163Thr	missense_variant	3/4	1	NM_001015052.3	P2
MPG	ENST00000219431.4	c.503T>C	p.Met168Thr	missense_variant	4/5	3		A2
MPG	ENST00000397817.5	c.452T>C	p.Met151Thr	missense_variant	3/4	2		A2
MPG	ENST00000436333.5	c.452T>C	p.Met151Thr	missense_variant	3/4	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 23, 2023

The c.503T>C (p.M168T) alteration is located in exon 4 (coding exon 3) of the MPG gene. This alteration results from a T to C substitution at nucleotide position 503, causing the methionine (M) at amino acid position 168 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.62
BayesDel_addAF	Benign	-0.033	T
BayesDel_noAF	Benign	-0.29
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.10	T;.;.;T
Eigen	Uncertain	0.62
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.91	D;D;D;D
M_CAP	Benign	0.022	T
MetaRNN	Uncertain	0.70	D;D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.6	.;.;.;M
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.66	T
PROVEAN	Uncertain	-3.6	D;D;D;D
REVEL	Benign	0.29
Sift	Uncertain	0.0090	D;D;D;D
Sift4G	Uncertain	0.015	D;D;D;D
Polyphen		0.88	P;.;.;P
Vest4		0.56, 0.58, 0.61
MutPred		0.76		.;.;.;Loss of stability (P = 0.0676);
MVP		0.60
MPC		0.30
ClinPred		0.98	D
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.87
gMVP		0.86

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-133238;