NM_024042.4:c.56C>T

Variant names:

• chr16-715345-C-T
• rs1485692105
• NM_024042.4:c.56C>T

Variant summary

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

The NM_024042.4(METRN):​c.56C>T​(p.Pro19Leu) 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. 15/21 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)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: METRN NM_024042.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.245
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.037807375).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024042.4. 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
	METRN	NM_024042.4	MANE Select	c.56C>T	p.Pro19Leu	missense	Exon 1 of 4	NP_076947.1	Q9UJH8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	METRN	ENST00000568223.7	TSL:1 MANE Select	c.56C>T	p.Pro19Leu	missense	Exon 1 of 4	ENSP00000455068.1	Q9UJH8
	METRN	ENST00000936477.1		c.56C>T	p.Pro19Leu	missense	Exon 1 of 4	ENSP00000606536.1
	METRN	ENST00000219542.3	TSL:2	c.8C>T	p.Pro3Leu	missense	Exon 1 of 3	ENSP00000219542.3	J3KMW6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1189388 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 579152

African (AFR) AF: 0.00 AC: 0 AN: 23628

American (AMR) AF: 0.00 AC: 0 AN: 11264

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17078

East Asian (EAS) AF: 0.00 AC: 0 AN: 26654

South Asian (SAS) AF: 0.00 AC: 0 AN: 51432

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 28300

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3290

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 979702

Other (OTH) AF: 0.00 AC: 0 AN: 48040

GnomAD4 genome Cov.: 33

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	0.12
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	15
DANN	Benign	0.91
DEOGEN2	Benign	0.0051	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.0091	N
LIST_S2	Benign	0.53	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.038	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.90	N
PhyloP100		-0.24
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	0.37	N
REVEL	Benign	0.035
Sift	Benign	0.20	T
Sift4G	Benign	0.38	T
Polyphen		0.0	B
Vest4		0.084
MutPred		0.35		Gain of helix (P = 0.005)
MVP		0.072
MPC		0.26
ClinPred		0.047	T
GERP RS		-2.2
PromoterAI		0.058	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.038
gMVP		0.25

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: rs1485692105; hg19: chr16-765345;