chr22-40681062-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_005297.4(MCHR1):c.196G>A(p.Val66Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000414 in 1,613,934 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_005297.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MCHR1 | NM_005297.4 | c.196G>A | p.Val66Met | missense_variant | 2/2 | ENST00000249016.5 | |
LOC124905123 | XR_007068110.1 | n.189-285C>T | intron_variant, non_coding_transcript_variant | ||||
LOC124905123 | XR_007068109.1 | n.3869C>T | non_coding_transcript_exon_variant | 1/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MCHR1 | ENST00000249016.5 | c.196G>A | p.Val66Met | missense_variant | 2/2 | 1 | NM_005297.4 | P1 | |
ENST00000688408.2 | n.198-285C>T | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes AF: 0.000289 AC: 44AN: 152044Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000254 AC: 64AN: 251484Hom.: 0 AF XY: 0.000228 AC XY: 31AN XY: 135914
GnomAD4 exome AF: 0.000427 AC: 624AN: 1461890Hom.: 0 Cov.: 32 AF XY: 0.000393 AC XY: 286AN XY: 727244
GnomAD4 genome AF: 0.000289 AC: 44AN: 152044Hom.: 0 Cov.: 32 AF XY: 0.000162 AC XY: 12AN XY: 74246
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 10, 2022 | The c.403G>A (p.V135M) alteration is located in exon 2 (coding exon 2) of the MCHR1 gene. This alteration results from a G to A substitution at nucleotide position 403, causing the valine (V) at amino acid position 135 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
MCHR1-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jul 14, 2023 | The MCHR1 c.403G>A variant is predicted to result in the amino acid substitution p.Val135Met. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.047% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/22-41077066-G-A). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at