16-715353-C-T

Variant names:

• chr16-715353-C-T
• NM_024042.4:c.64C>T

Variant summary

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

The NM_024042.4(METRN):​c.64C>T​(p.Arg22Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000337 in 1,188,262 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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: 0.0000034 (0 hom.)
• Consequence: METRN NM_024042.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.157
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10975373).

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.64C>T	p.Arg22Cys	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.64C>T	p.Arg22Cys	missense	Exon 1 of 4	ENSP00000455068.1	Q9UJH8
	METRN	ENST00000936477.1		c.64C>T	p.Arg22Cys	missense	Exon 1 of 4	ENSP00000606536.1
	METRN	ENST00000219542.3	TSL:2	c.16C>T	p.Arg6Cys	missense	Exon 1 of 3	ENSP00000219542.3	J3KMW6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000337 AC: 4 AN: 1188262 Hom.: 0 Cov.: 31 AF XY: 0.00000346 AC XY: 2 AN XY: 578422

African (AFR) AF: 0.00 AC: 0 AN: 23640

American (AMR) AF: 0.00 AC: 0 AN: 11044

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17000

East Asian (EAS) AF: 0.00 AC: 0 AN: 26710

South Asian (SAS) AF: 0.00 AC: 0 AN: 51070

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 28200

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3280

European-Non Finnish (NFE) AF: 0.00000408 AC: 4 AN: 979284

Other (OTH) AF: 0.00 AC: 0 AN: 48034

GnomAD4 genome Cov.: 33

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	0.21
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	18
DANN	Benign	0.87
DEOGEN2	Benign	0.0042	T
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.46
FATHMM_MKL	Benign	0.084	N
LIST_S2	Benign	0.53	T
M_CAP	Uncertain	0.089	D
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L
PhyloP100		0.16
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-0.17	N
REVEL	Benign	0.055
Sift	Benign	0.18	T
Sift4G	Benign	0.21	T
Polyphen		0.99	D
Vest4		0.079
MutPred		0.31		Loss of solvent accessibility (P = 0.0079)
MVP		0.16
MPC		0.35
ClinPred		0.26	T
GERP RS		2.3
PromoterAI		0.035	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.3
Varity_R		0.064
gMVP		0.31
Mutation Taster		=98/2	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

hg19: chr16-765353;