11-92981719-C-G

Variant names:

• chr11-92981719-C-G
• rs185167892
• NM_005959.5:c.496C>G

Variant summary

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

The NM_005959.5(MTNR1B):​c.496C>G​(p.Leu166Val) 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. 16/22 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)
• Consequence: MTNR1B NM_005959.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.389
• Publications: 2 publications found

Genes affected

MTNR1B (HGNC:7464): (melatonin receptor 1B) This gene encodes one of two high affinity forms of a receptor for melatonin, the primary hormone secreted by the pineal gland. This gene product is an integral membrane protein that is a G-protein coupled, 7-transmembrane receptor. It is found primarily in the retina and brain although this detection requires RT-PCR. It is thought to participate in light-dependent functions in the retina and may be involved in the neurobiological effects of melatonin. [provided by RefSeq, Jul 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=0.10206506).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005959.5. 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
	MTNR1B	NM_005959.5	MANE Select	c.496C>G	p.Leu166Val	missense	Exon 2 of 2	NP_005950.1	P49286

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTNR1B	ENST00000257068.3	TSL:1 MANE Select	c.496C>G	p.Leu166Val	missense	Exon 2 of 2	ENSP00000257068.2	P49286
	MTNR1B	ENST00000528076.1	TSL:3	c.165-3088C>G		intron	N/A	ENSP00000433573.1	H0YDG4
	MTNR1B	ENST00000532482.1	TSL:5	n.*387C>G		non_coding_transcript_exon	Exon 3 of 3	ENSP00000436101.1	E9PR36

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions as Germline

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	0.11
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	10
DANN	Benign	0.058
DEOGEN2	Benign	0.052	T
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.50
FATHMM_MKL	Benign	0.56	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.0015	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.56	N
PhyloP100		0.39
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.40	N
REVEL	Benign	0.12
Sift	Benign	0.93	T
Sift4G	Benign	0.77	T
Polyphen		0.017	B
Vest4		0.063
MutPred		0.65		Loss of stability (P = 0.0956)
MVP		0.44
MPC		0.18
ClinPred		0.10	T
GERP RS		3.0
Varity_R		0.089
gMVP		0.11
Mutation Taster		=85/15	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

dbSNP: rs185167892; hg19: chr11-92714885;