11-92969946-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_005959.5(MTNR1B):c.221C>T(p.Ala74Val) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000746 in 1,607,964 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_005959.5 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MTNR1B | NM_005959.5 | c.221C>T | p.Ala74Val | missense_variant, splice_region_variant | Exon 1 of 2 | ENST00000257068.3 | NP_005950.1 | |
MTNR1B | XM_011542839.3 | c.221C>T | p.Ala74Val | missense_variant, splice_region_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.221C>T | p.Ala74Val | missense_variant, splice_region_variant | Exon 1 of 2 | 1 | NM_005959.5 | ENSP00000257068.2 | ||
MTNR1B | ENST00000528076.1 | c.162C>T | p.Arg54Arg | splice_region_variant, synonymous_variant | Exon 1 of 2 | 3 | ENSP00000433573.1 | |||
MTNR1B | ENST00000532482.1 | n.221C>T | splice_region_variant, non_coding_transcript_exon_variant | Exon 1 of 3 | 5 | ENSP00000436101.1 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152196Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000125 AC: 3AN: 239052Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 130368
GnomAD4 exome AF: 0.00000550 AC: 8AN: 1455768Hom.: 0 Cov.: 32 AF XY: 0.00000553 AC XY: 4AN XY: 723556
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152196Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74364
ClinVar
Submissions by phenotype
not specified Uncertain:1
The c.221C>T (p.A74V) alteration is located in exon 1 (coding exon 1) of the MTNR1B gene. This alteration results from a C to T substitution at nucleotide position 221, causing the alanine (A) at amino acid position 74 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at