rs1858108744

Variant names:

• chr11-92981759-G-A
• rs1858108744
• NM_005959.5:c.536G>A

Your query was ambiguous. Multiple possible variants found:

• chr11-92981759-G-A
• chr11-92981759-G-T

Variant summary

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

The NM_005959.5(MTNR1B):​c.536G>A​(p.Gly179Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. G179V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: MTNR1B NM_005959.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.96
• Publications: 0 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.536G>A	p.Gly179Glu	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.536G>A	p.Gly179Glu	missense	Exon 2 of 2	ENSP00000257068.2	P49286
	MTNR1B	ENST00000528076.1	TSL:3	c.165-3048G>A		intron	N/A	ENSP00000433573.1	H0YDG4
	MTNR1B	ENST00000532482.1	TSL:5	n.*427G>A		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

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.62
BayesDel_addAF	Benign	-0.052	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.46	T
Eigen	Benign	0.17
Eigen_PC	Benign	0.14
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.0080	T
MetaRNN	Uncertain	0.42	T
MetaSVM	Benign	-0.83	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		3.0
PrimateAI	Uncertain	0.60	T
PROVEAN	Pathogenic	-6.2	D
REVEL	Benign	0.23
Sift	Benign	0.066	T
Sift4G	Benign	0.19	T
Polyphen		0.59	P
Vest4		0.21
MutPred		0.78		Gain of relative solvent accessibility (P = 0.09)
MVP		0.65
MPC		0.36
ClinPred		0.98	D
GERP RS		3.0
Varity_R		0.58
gMVP		0.53
Mutation Taster		=66/34	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: rs1858108744; hg19: chr11-92714925;