rs1485692105

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr16-715345-C-A
• chr16-715345-C-G
• chr16-715345-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_024042.4(METRN):​c.56C>A​(p.Pro19Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000252 in 1,189,388 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P19L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000025 (0 hom.)
• Consequence: METRN NM_024042.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.245

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03953162).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
METRN	NM_024042.4	c.56C>A	p.Pro19Gln	missense_variant	Exon 1 of 4	ENST00000568223.7	NP_076947.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
METRN	ENST00000568223.7	c.56C>A	p.Pro19Gln	missense_variant	Exon 1 of 4	1	NM_024042.4	ENSP00000455068.1
METRN	ENST00000219542.3	c.8C>A	p.Pro3Gln	missense_variant	Exon 1 of 3	2		ENSP00000219542.3
METRN	ENST00000570132.1	n.56C>A		non_coding_transcript_exon_variant	Exon 1 of 4	3		ENSP00000456647.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.0000621 AC: 1 AN: 16098 Hom.: 0 AF XY: 0.0000988 AC XY: 1 AN XY: 10124

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000171

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000252 AC: 3 AN: 1189388 Hom.: 0 Cov.: 31 AF XY: 0.00000173 AC XY: 1 AN XY: 579152

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000306

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	13
DANN	Benign	0.82
DEOGEN2	Benign	0.0051	T;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.048	N
LIST_S2	Benign	0.40	T;T
M_CAP	Benign	0.0077	T
MetaRNN	Benign	0.040	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N;.
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	0.65	N;N
REVEL	Benign	0.075
Sift	Benign	0.27	T;T
Sift4G	Benign	0.60	T;T
Polyphen		0.19	B;.
Vest4		0.20
MutPred		0.27		Gain of helix (P = 0.0078);.;
MVP		0.030
MPC		0.24
ClinPred		0.027	T
GERP RS		-2.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.040
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

Publications

LitVar

Other links and lift over

dbSNP: rs1485692105; hg19: chr16-765345;