16-715820-C-G

Position:

• chr16-715820-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000568223.7(METRN):​c.341C>G​(p.Ala114Gly) 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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: METRN ENST00000568223.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.938

Genes affected

METRN (HGNC:14151): (meteorin, glial cell differentiation regulator) Meteorin regulates glial cell differentiation and promotes the formation of axonal networks during neurogenesis (Nishino et al., 2004 [PubMed 15085178]).[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07989946).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
METRN	NM_024042.4	c.341C>G	p.Ala114Gly	missense_variant	2/4	ENST00000568223.7	NP_076947.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
METRN	ENST00000568223.7	c.341C>G	p.Ala114Gly	missense_variant	2/4	1	NM_024042.4	ENSP00000455068.1
METRN	ENST00000219542.3	c.293C>G	p.Ala98Gly	missense_variant	2/3	2		ENSP00000219542.3
METRN	ENST00000567076.5	c.179C>G	p.Ala60Gly	missense_variant	1/4	5		ENSP00000459900.1
METRN	ENST00000570132.1	n.105-56C>G		intron_variant		3		ENSP00000456647.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

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

Jun 07, 2024

The c.341C>G (p.A114G) alteration is located in exon 2 (coding exon 2) of the METRN gene. This alteration results from a C to G substitution at nucleotide position 341, causing the alanine (A) at amino acid position 114 to be replaced by a glycine (G). 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	Benign	0.079
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	16
DANN	Benign	0.85
DEOGEN2	Benign	0.0053	T;T
Eigen	Benign	-0.85
Eigen_PC	Benign	-0.85
FATHMM_MKL	Benign	0.25	N
LIST_S2	Benign	0.63	T;T
M_CAP	Benign	0.047	D
MetaRNN	Benign	0.080	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.5	L;.
MutationTaster	Benign	1.0	N;D;D
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-0.80	N;N
REVEL	Benign	0.064
Sift	Benign	0.42	T;T
Sift4G	Benign	0.28	T;T
Polyphen		0.0020	B;.
Vest4		0.12
MutPred		0.15		Gain of disorder (P = 0.1076);.;
MVP		0.13
MPC		0.30
ClinPred		0.18	T
GERP RS		3.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.15
gMVP		0.37

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: rs2040156480; hg19: chr16-765820;