NM_020203.6:c.304A>G

Variant names:

• chr4-87845172-A-G
• rs1723167652
• NM_020203.6:c.304A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020203.6(MEPE):​c.304A>G​(p.Ile102Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,461,358 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: MEPE NM_020203.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.564
• Publications: 0 publications found

Genes affected

MEPE (HGNC:13361): (matrix extracellular phosphoglycoprotein) This gene encodes a secreted calcium-binding phosphoprotein that belongs to the small integrin-binding ligand, N-linked glycoprotein (SIBLING) family of proteins. Members of this family are components of the extracellular matrix of bone and dentin and regulate bone mineralization. Deficiency of a similar protein in mouse results in increased bone mass. Mice lacking this gene are resistant to aging-related trabecular bone loss. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2014]

ENSG00000307815 (HGNC:58843):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.079370886).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020203.6. 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
	MEPE	NM_020203.6	MANE Select	c.304A>G	p.Ile102Val	missense	Exon 4 of 4	NP_064588.1	Q9NQ76-1
	MEPE	NM_001291183.2		c.397A>G	p.Ile133Val	missense	Exon 5 of 5	NP_001278112.1	Q9NQ76-2
	MEPE	NM_001184694.3		c.304A>G	p.Ile102Val	missense	Exon 4 of 4	NP_001171623.1	Q9NQ76-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MEPE	ENST00000361056.4	TSL:1 MANE Select	c.304A>G	p.Ile102Val	missense	Exon 4 of 4	ENSP00000354341.3	Q9NQ76-1
	MEPE	ENST00000560249.6	TSL:1	c.*122A>G		3_prime_UTR	Exon 6 of 6	ENSP00000453994.2	A0A8J9B5S1
	MEPE	ENST00000395102.8	TSL:5	c.397A>G	p.Ile133Val	missense	Exon 5 of 5	ENSP00000378534.4	Q9NQ76-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000411 AC: 6 AN: 1461358 Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5 AN XY: 726986

African (AFR) AF: 0.00 AC: 0 AN: 33450

American (AMR) AF: 0.00 AC: 0 AN: 44666

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26118

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.00 AC: 0 AN: 86200

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53400

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00000540 AC: 6 AN: 1111704

Other (OTH) AF: 0.00 AC: 0 AN: 60370

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

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	0.093
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.37
DANN	Benign	0.22
DEOGEN2	Benign	0.085	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.031	N
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.0062	T
MetaRNN	Benign	0.079	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
PhyloP100		0.56
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.22	N
REVEL	Benign	0.049
Sift	Benign	0.38	T
Sift4G	Benign	0.41	T
Polyphen		0.033	B
Vest4		0.026
MutPred		0.62		Gain of MoRF binding (P = 0.1152)
MVP		0.17
MPC		0.035
ClinPred		0.079	T
GERP RS		-1.9
Varity_R		0.021
gMVP		0.035
Mutation Taster		=99/1	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: rs1723167652; hg19: chr4-88766324;