chr17-83079838-C-T

Variant names:

• chr17-83079838-C-T
• NM_001004431.3:c.23C>T

Variant summary

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

The NM_001004431.3(METRNL):​c.23C>T​(p.Ala8Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000012 in 830,286 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000012 (0 hom.)
• Consequence: METRNL NM_001004431.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.275

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

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=0.064815074).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
METRNL	NM_001004431.3	c.23C>T	p.Ala8Val	missense_variant	Exon 1 of 4	ENST00000320095.12	NP_001004431.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
METRNL	ENST00000320095.12	c.23C>T	p.Ala8Val	missense_variant	Exon 1 of 4	1	NM_001004431.3	ENSP00000315731.6

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000120 AC: 1 AN: 830286 Hom.: 0 Cov.: 26 AF XY: 0.00000261 AC XY: 1 AN XY: 383516

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: 0.0000590

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 07, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.23C>T (p.A8V) alteration is located in exon 1 (coding exon 1) of the METRNL gene. This alteration results from a C to T substitution at nucleotide position 23, causing the alanine (A) at amino acid position 8 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	17
DANN	Benign	0.94
DEOGEN2	Benign	0.019	T
Eigen	Benign	-0.88
Eigen_PC	Benign	-0.86
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.39	T
M_CAP	Uncertain	0.13	D
MetaRNN	Benign	0.065	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.0	L
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	0.12	N
REVEL	Benign	0.026
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.85	T
Polyphen		0.0010	B
Vest4		0.19
MutPred		0.25		Loss of helix (P = 0.0444);
MVP		0.043
MPC		0.54
ClinPred		0.11	T
GERP RS		0.45
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.11
gMVP		0.37

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-81037714;