17-31360548-C-T
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PP2BP4BS2_Supporting
The NM_001042492.3(NF1):c.8222C>T(p.Thr2741Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000684 in 1,461,852 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T2741K) has been classified as Uncertain significance.
Frequency
Consequence
NM_001042492.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NF1 | NM_001042492.3 | c.8222C>T | p.Thr2741Met | missense_variant | 57/58 | ENST00000358273.9 | |
NF1 | NM_000267.3 | c.8159C>T | p.Thr2720Met | missense_variant | 56/57 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NF1 | ENST00000358273.9 | c.8222C>T | p.Thr2741Met | missense_variant | 57/58 | 1 | NM_001042492.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00 AC: 1AN: 152100Hom.: 0 Cov.: 32 FAILED QC
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251450Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135896
GnomAD4 exome AF: 0.00000684 AC: 10AN: 1461852Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4AN XY: 727230
GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000657 AC: 1AN: 152100Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74294
ClinVar
Submissions by phenotype
Neurofibromatosis, type 1 Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Sep 22, 2023 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Mar 15, 2022 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Feb 01, 2019 | - - |
Juvenile myelomonocytic leukemia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Nov 08, 2019 | This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. - |
Hereditary cancer-predisposing syndrome;CN230736:Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 19, 2021 | The c.8159C>T (p.T2720M) alteration is located in exon 56 (coding exon 56) of the NF1 gene. This alteration results from a C to T substitution at nucleotide position 8159, causing the threonine (T) at amino acid position 2720 to be replaced by a methionine (M). 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