chr4-186534140-A-G

Variant names:

• chr4-186534140-A-G
• NM_005958.4:c.602T>C

Variant summary

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

The NM_005958.4(MTNR1A):​c.602T>C​(p.Ile201Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,554 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: MTNR1A NM_005958.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.63

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07572624).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTNR1A	NM_005958.4	c.602T>C	p.Ile201Thr	missense_variant	Exon 2 of 2	ENST00000307161.5	NP_005949.1
MTNR1A	XM_011532002.4	c.347T>C	p.Ile116Thr	missense_variant	Exon 2 of 2		XP_011530304.1
LOC105377596	XR_007058498.1	n.143+9245A>G		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTNR1A	ENST00000307161.5	c.602T>C	p.Ile201Thr	missense_variant	Exon 2 of 2	1	NM_005958.4	ENSP00000302811.5
ENSG00000272297	ENST00000509111.2	c.145+21042T>C		intron_variant	Intron 1 of 1	3		ENSP00000422449.2
MTNR1A	ENST00000703170.1	c.602T>C	p.Ile201Thr	missense_variant	Exon 2 of 2			ENSP00000515216.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461554 Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4 AN XY: 727022

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000360

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	7.5
DANN	Benign	0.33
DEOGEN2	Benign	0.052	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.33	N
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.0026	T
MetaRNN	Benign	0.076	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.59	N
PrimateAI	Benign	0.31	T
PROVEAN	Benign	1.1	N
REVEL	Benign	0.042
Sift	Benign	0.62	T
Sift4G	Benign	0.50	T
Polyphen		0.0	B
Vest4		0.074
MutPred		0.65		Loss of stability (P = 0.0134);
MVP		0.33
MPC		0.32
ClinPred		0.034	T
GERP RS		-0.011
Varity_R		0.037
gMVP		0.32

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: chr4-187455294;