4-186555206-G-C

Variant names:

• chr4-186555206-G-C
• rs1800885
• NM_005958.4:c.160C>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_005958.4(MTNR1A):​c.160C>G​(p.Arg54Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,252 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 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. R54W) has been classified as Likely benign.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: MTNR1A NM_005958.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.917

Genes affected

MTNR1A (HGNC:7463): (melatonin receptor 1A) This gene encodes one of two high affinity forms of a receptor for melatonin, the primary hormone secreted by the pineal gland. This receptor is a G-protein coupled, 7-transmembrane receptor that is responsible for melatonin effects on mammalian circadian rhythm and reproductive alterations affected by day length. The receptor is an integral membrane protein that is readily detectable and localized to two specific regions of the brain. The hypothalamic suprachiasmatic nucleus appears to be involved in circadian rhythm while the hypophysial pars tuberalis may be responsible for the reproductive effects of melatonin. [provided by RefSeq, Jul 2008]

ENSG00000272297 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29824254).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTNR1A	NM_005958.4	c.160C>G	p.Arg54Gly	missense_variant	Exon 1 of 2	ENST00000307161.5	NP_005949.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTNR1A	ENST00000307161.5	c.160C>G	p.Arg54Gly	missense_variant	Exon 1 of 2	1	NM_005958.4	ENSP00000302811.5
ENSG00000272297	ENST00000509111.2	c.121C>G	p.Arg41Gly	missense_variant	Exon 1 of 2	3		ENSP00000422449.2
MTNR1A	ENST00000703170.1	c.160C>G	p.Arg54Gly	missense_variant	Exon 1 of 2			ENSP00000515216.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152134 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00000459 AC: 1 AN: 217858 Hom.: 0 AF XY: 0.00000848 AC XY: 1 AN XY: 117908

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000185

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152252 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74438

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.46
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.030
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.39	T
Eigen	Benign	-0.036
Eigen_PC	Benign	0.038
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.067	D
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Uncertain	2.6	M
PrimateAI	Uncertain	0.61	T
PROVEAN	Uncertain	-3.7	D
REVEL	Benign	0.27
Sift	Benign	0.071	T
Sift4G	Benign	0.31	T
Polyphen		0.050	B
Vest4		0.44
MutPred		0.66		Loss of stability (P = 0.0063);
MVP		0.72
MPC		0.42
ClinPred		0.97	D
GERP RS		3.8
Varity_R		0.38
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

LitVar

Other links and lift over

dbSNP: rs1800885; hg19: chr4-187476360;