rs139336504
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2
The NM_015166.4(MLC1):c.1008G>T(p.Gln336His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00015 in 1,609,726 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_015166.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MLC1 | NM_015166.4 | c.1008G>T | p.Gln336His | missense_variant | 11/12 | ENST00000311597.10 | NP_055981.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MLC1 | ENST00000311597.10 | c.1008G>T | p.Gln336His | missense_variant | 11/12 | 1 | NM_015166.4 | ENSP00000310375.6 | ||
MLC1 | ENST00000395876.6 | c.1008G>T | p.Gln336His | missense_variant | 11/12 | 1 | ENSP00000379216.2 | |||
MLC1 | ENST00000483836.1 | n.365G>T | non_coding_transcript_exon_variant | 4/5 | 2 |
Frequencies
GnomAD3 genomes AF: 0.000178 AC: 27AN: 151604Hom.: 2 Cov.: 34
GnomAD3 exomes AF: 0.000190 AC: 47AN: 247902Hom.: 0 AF XY: 0.000178 AC XY: 24AN XY: 134734
GnomAD4 exome AF: 0.000147 AC: 214AN: 1458122Hom.: 6 Cov.: 39 AF XY: 0.000135 AC XY: 98AN XY: 725594
GnomAD4 genome AF: 0.000178 AC: 27AN: 151604Hom.: 2 Cov.: 34 AF XY: 0.000203 AC XY: 15AN XY: 74032
ClinVar
Submissions by phenotype
Megalencephalic leukoencephalopathy with subcortical cysts 1 Uncertain:3
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Jul 31, 2018 | This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | May 30, 2017 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Dec 13, 2021 | - - |
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Sep 07, 2022 | This sequence change replaces glutamine, which is neutral and polar, with histidine, which is basic and polar, at codon 336 of the MLC1 protein (p.Gln336His). This variant is present in population databases (rs139336504, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with MLC1-related conditions. ClinVar contains an entry for this variant (Variation ID: 547978). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Uncertain significance, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 10, 2024 | The c.1008G>T (p.Q336H) alteration is located in exon 11 (coding exon 10) of the MLC1 gene. This alteration results from a G to T substitution at nucleotide position 1008, causing the glutamine (Q) at amino acid position 336 to be replaced by a histidine (H). 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