Variant chr4-186533797-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_005958.4(MTNR1A):c.945A>G(p.Thr315=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0466 in 1,614,108 control chromosomes in the GnomAD database, including 2,214 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.059 ( 360 hom., cov: 32)

Exomes 𝑓: 0.045 ( 1854 hom. )

Consequence

MTNR1A
NM_005958.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.315

Variant links:

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]

MTNR1A links:

LOC105377596 (HGNC:):

LOC105377596 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP6

Variant 4-186533797-T-C is Benign according to our data. Variant chr4-186533797-T-C is described in ClinVar as [Benign]. Clinvar id is 1252210.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.315 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.106 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MTNR1A	NM_005958.4 linkuse as main transcript	c.945A>G	p.Thr315=	synonymous_variant	2/2	ENST00000307161.5	NP_005949.1
LOC105377596	XR_007058498.1 linkuse as main transcript	n.143+8902T>C		intron_variant, non_coding_transcript_variant
MTNR1A	XM_011532002.4 linkuse as main transcript	c.690A>G	p.Thr230=	synonymous_variant	2/2		XP_011530304.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTNR1A	ENST00000307161.5 linkuse as main transcript	c.945A>G	p.Thr315=	synonymous_variant	2/2	1	NM_005958.4	ENSP00000302811	P1
MTNR1A	ENST00000703170.1 linkuse as main transcript	c.945A>G	p.Thr315=	synonymous_variant	2/2			ENSP00000515216	P1

Frequencies

GnomAD3 genomes

AF:

0.0593

AC:

9021

AN:

152152

Hom.:

353

Cov.:

show subpopulations

Gnomad AFR

AF:

0.108

Gnomad AMI

AF:

0.0274

Gnomad AMR

AF:

0.0454

Gnomad ASJ

AF:

0.0228

Gnomad EAS

AF:

0.0790

Gnomad SAS

AF:

0.0380

Gnomad FIN

AF:

0.00546

Gnomad MID

AF:

0.0633

Gnomad NFE

AF:

0.0433

Gnomad OTH

AF:

0.0588

GnomAD3 exomes

AF:

0.0422

AC:

10609

AN:

251494

Hom.:

330

AF XY:

0.0418

AC XY:

5677

AN XY:

135922

show subpopulations

Gnomad AFR exome

AF:

0.110

Gnomad AMR exome

AF:

0.0253

Gnomad ASJ exome

AF:

0.0222

Gnomad EAS exome

AF:

0.0785

Gnomad SAS exome

AF:

0.0375

Gnomad FIN exome

AF:

0.00661

Gnomad NFE exome

AF:

0.0415

Gnomad OTH exome

AF:

0.0436

GnomAD4 exome

AF:

0.0453

AC:

66166

AN:

1461838

Hom.:

1854

Cov.:

AF XY:

0.0451

AC XY:

32798

AN XY:

727210

show subpopulations

Gnomad4 AFR exome

AF:

0.105

Gnomad4 AMR exome

AF:

0.0279

Gnomad4 ASJ exome

AF:

0.0216

Gnomad4 EAS exome

AF:

0.0939

Gnomad4 SAS exome

AF:

0.0399

Gnomad4 FIN exome

AF:

0.00760

Gnomad4 NFE exome

AF:

0.0448

Gnomad4 OTH exome

AF:

0.0526

GnomAD4 genome

AF:

0.0594

AC:

9047

AN:

152270

Hom.:

360

Cov.:

AF XY:

0.0565

AC XY:

4204

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.109

Gnomad4 AMR

AF:

0.0454

Gnomad4 ASJ

AF:

0.0228

Gnomad4 EAS

AF:

0.0790

Gnomad4 SAS

AF:

0.0384

Gnomad4 FIN

AF:

0.00546

Gnomad4 NFE

AF:

0.0433

Gnomad4 OTH

AF:

0.0577

Alfa

AF:

0.0402

Hom.:

Bravo

AF:

0.0648

Asia WGS

AF:

0.0590

AC:

206

AN:

3478

EpiCase

AF:

0.0489

EpiControl

AF:

0.0456

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

2.5

DANN

Benign

0.29

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over