16-715762-T-C

Variant names:

• chr16-715762-T-C
• NM_024042.4:c.283T>C
• METRN p.Phe95Leu

Variant summary

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

The NM_024042.4(METRN):​c.283T>C​(p.Phe95Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: METRN NM_024042.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.83
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.283T>C	p.Phe95Leu	missense	Exon 2 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.283T>C	p.Phe95Leu	missense	Exon 2 of 4	ENSP00000455068.1	Q9UJH8
	METRN	ENST00000936477.1		c.307T>C	p.Phe103Leu	missense	Exon 2 of 4	ENSP00000606536.1
	METRN	ENST00000219542.3	TSL:2	c.235T>C	p.Phe79Leu	missense	Exon 2 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: 1115630 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 534554

African (AFR) AF: 0.00 AC: 0 AN: 22580

American (AMR) AF: 0.00 AC: 0 AN: 8116

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14332

East Asian (EAS) AF: 0.00 AC: 0 AN: 25658

South Asian (SAS) AF: 0.00 AC: 0 AN: 31346

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 23702

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2982

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 942230

Other (OTH) AF: 0.00 AC: 0 AN: 44684

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.96
BayesDel_addAF	Benign	-0.017	T
BayesDel_noAF	Benign	-0.26
CADD	Uncertain	23
DANN	Benign	0.97
DEOGEN2	Benign	0.21	T
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.20
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.70	T
M_CAP	Uncertain	0.18	D
MetaRNN	Uncertain	0.44	T
MetaSVM	Benign	-0.88	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		2.8
PrimateAI	Pathogenic	0.96	D
PROVEAN	Uncertain	-3.9	D
REVEL	Benign	0.10
Sift	Benign	0.052	T
Sift4G	Benign	0.10	T
PromoterAI		0.068	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.35
gMVP		0.66

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr16-765762;