rs781742897
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_030962.4(SBF2):c.3001A>T(p.Met1001Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000254 in 1,613,802 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M1001I) has been classified as Uncertain significance.
Frequency
Consequence
NM_030962.4 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 |
---|---|---|---|---|---|---|---|
SBF2 | NM_030962.4 | c.3001A>T | p.Met1001Leu | missense_variant | 24/40 | ENST00000256190.13 | |
LOC101928008 | NR_120539.1 | n.135+6398T>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SBF2 | ENST00000256190.13 | c.3001A>T | p.Met1001Leu | missense_variant | 24/40 | 1 | NM_030962.4 | P3 | |
ENST00000533659.1 | n.134+6398T>A | intron_variant, non_coding_transcript_variant | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152178Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000477 AC: 12AN: 251326Hom.: 0 AF XY: 0.0000810 AC XY: 11AN XY: 135816
GnomAD4 exome AF: 0.0000267 AC: 39AN: 1461624Hom.: 0 Cov.: 31 AF XY: 0.0000385 AC XY: 28AN XY: 727128
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152178Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74356
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 25, 2020 | The p.M1001L variant (also known as c.3001A>T), located in coding exon 24 of the SBF2 gene, results from an A to T substitution at nucleotide position 3001. The methionine at codon 1001 is replaced by leucine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Charcot-Marie-Tooth disease type 4B2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
Charcot-Marie-Tooth disease type 4 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 08, 2020 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with SBF2-related disease. ClinVar contains an entry for this variant (Variation ID: 306590). This variant is present in population databases (rs781742897, ExAC 0.05%). This sequence change replaces methionine with leucine at codon 1001 of the SBF2 protein (p.Met1001Leu). The methionine residue is moderately conserved and there is a small physicochemical difference between methionine and leucine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at