chr11-92969759-G-C

Variant names:

• chr11-92969759-G-C
• NM_005959.5:c.34G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005959.5(MTNR1B):​c.34G>C​(p.Glu12Gln) 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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MTNR1B NM_005959.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.21

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08583623).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTNR1B	NM_005959.5	c.34G>C	p.Glu12Gln	missense_variant	Exon 1 of 2	ENST00000257068.3	NP_005950.1
MTNR1B	XM_011542839.3	c.34G>C	p.Glu12Gln	missense_variant	Exon 1 of 3		XP_011541141.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTNR1B	ENST00000257068.3	c.34G>C	p.Glu12Gln	missense_variant	Exon 1 of 2	1	NM_005959.5	ENSP00000257068.2
MTNR1B	ENST00000532482.1	n.34G>C		non_coding_transcript_exon_variant	Exon 1 of 3	5		ENSP00000436101.1
MTNR1B	ENST00000528076.1	c.-26G>C		upstream_gene_variant		3		ENSP00000433573.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	14
DANN	Uncertain	0.99
DEOGEN2	Benign	0.084	T
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.69
FATHMM_MKL	Benign	0.33	N
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.052	D
MetaRNN	Benign	0.086	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	1.2	L
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-0.75	N
REVEL	Benign	0.13
Sift	Uncertain	0.025	D
Sift4G	Benign	0.31	T
Polyphen		0.010	B
Vest4		0.18
MutPred		0.29		Gain of MoRF binding (P = 0.0245);
MVP		0.81
MPC		0.16
ClinPred		0.62	D
GERP RS		3.3
Varity_R		0.15
gMVP		0.71

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: chr11-92702925;