rs2165668

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000509111.2(ENSG00000272297):​c.145+21635A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000103 in 966,202 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.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000010 ( 0 hom. )

Consequence

ENSG00000272297
ENST00000509111.2 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.21
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.96).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
LOC105377596XR_007058498.1 linkn.143+8652T>A intron_variant Intron 2 of 2
MTNR1ANM_005958.4 linkc.*142A>T downstream_gene_variant ENST00000307161.5 NP_005949.1 P48039
MTNR1AXM_011532002.4 linkc.*142A>T downstream_gene_variant XP_011530304.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ENSG00000272297ENST00000509111.2 linkc.145+21635A>T intron_variant Intron 1 of 1 3 ENSP00000422449.2 H0Y8X5
MTNR1AENST00000703170 linkc.*142A>T 3_prime_UTR_variant Exon 2 of 2 ENSP00000515216.1 P48039
MTNR1AENST00000307161.5 linkc.*142A>T downstream_gene_variant 1 NM_005958.4 ENSP00000302811.5 P48039

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000103
AC:
1
AN:
966202
Hom.:
0
AF XY:
0.00000202
AC XY:
1
AN XY:
494820
show subpopulations
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:
0.0000147
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.96
CADD
Benign
0.074
DANN
Benign
0.31

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: chr4-187454701; API