chr16-715670-C-A

Variant names:

• chr16-715670-C-A
• NM_024042.4:c.191C>A

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_024042.4(METRN):​c.191C>A​(p.Ala64Glu) 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 pathogenic 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: 2.86
• 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_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.95

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.191C>A	p.Ala64Glu	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.191C>A	p.Ala64Glu	missense	Exon 2 of 4	ENSP00000455068.1	Q9UJH8
	METRN	ENST00000936477.1		c.215C>A	p.Ala72Glu	missense	Exon 2 of 4	ENSP00000606536.1
	METRN	ENST00000219542.3	TSL:2	c.143C>A	p.Ala48Glu	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: 1274048 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 628400

African (AFR) AF: 0.00 AC: 0 AN: 25522

American (AMR) AF: 0.00 AC: 0 AN: 20100

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21218

East Asian (EAS) AF: 0.00 AC: 0 AN: 27606

South Asian (SAS) AF: 0.00 AC: 0 AN: 66004

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31458

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3916

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1026096

Other (OTH) AF: 0.00 AC: 0 AN: 52128

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	Pathogenic	0.74
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.14
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.47	T
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.84	T
M_CAP	Pathogenic	0.53	D
MetaRNN	Pathogenic	0.95	D
MetaSVM	Benign	-0.45	T
MutationAssessor	Pathogenic	3.3	M
PhyloP100		2.9
PrimateAI	Pathogenic	0.92	D
PROVEAN	Pathogenic	-4.6	D
REVEL	Uncertain	0.56
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.80
MutPred		0.85		Gain of sheet (P = 0.0827)
MVP		0.23
MPC		1.0
ClinPred		1.0	D
GERP RS		2.9
PromoterAI		-0.020	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.83
gMVP		0.95

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: chr16-765670;