NM_001004431.3:c.292T>C

Variant names:

• chr17-83085059-T-C
• rs2038034269
• NM_001004431.3:c.292T>C
• METRNL p.Phe98Leu

Variant summary

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

The NM_001004431.3(METRNL):​c.292T>C​(p.Phe98Leu) 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. 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)
• Consequence: METRNL NM_001004431.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0330
• Publications: 0 publications found

Genes affected

METRNL (HGNC:27584): (meteorin like, glial cell differentiation regulator) Predicted to enable hormone activity. Predicted to be involved in several processes, including brown fat cell differentiation; energy homeostasis; and positive regulation of brown fat cell differentiation. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

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=0.027094722).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004431.3. 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
	METRNL	NM_001004431.3	MANE Select	c.292T>C	p.Phe98Leu	missense	Exon 2 of 4	NP_001004431.1	Q641Q3-1
	METRNL	NM_001363853.2		c.46T>C	p.Phe16Leu	missense	Exon 3 of 5	NP_001350782.1	Q641Q3-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	METRNL	ENST00000320095.12	TSL:1 MANE Select	c.292T>C	p.Phe98Leu	missense	Exon 2 of 4	ENSP00000315731.6	Q641Q3-1
	METRNL	ENST00000571814.1	TSL:1	c.46T>C	p.Phe16Leu	missense	Exon 1 of 3	ENSP00000460798.1	Q641Q3-2
	METRNL	ENST00000570778.5	TSL:5	c.46T>C	p.Phe16Leu	missense	Exon 2 of 4	ENSP00000458566.1	Q641Q3-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.62
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	6.6
DANN	Benign	0.61
DEOGEN2	Benign	0.014	T
Eigen	Benign	-0.89
Eigen_PC	Benign	-0.85
FATHMM_MKL	Benign	0.043	N
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.0028	T
MetaRNN	Benign	0.027	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L
PhyloP100		0.033
PrimateAI	Benign	0.41	T
PROVEAN	Benign	0.15	N
REVEL	Benign	0.026
Sift	Benign	0.75	T
Sift4G	Benign	1.0	T
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.071
gMVP		0.30

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

dbSNP: rs2038034269;

hg19: chr17-81042935;