18-48950171-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_005904.4(SMAD7):c.254C>T(p.Ala85Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 151,918 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 (★). Synonymous variant affecting the same amino acid position (i.e. A85A) has been classified as Likely benign.
Frequency
Consequence
NM_005904.4 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 |
---|---|---|---|---|---|---|---|
SMAD7 | NM_005904.4 | c.254C>T | p.Ala85Val | missense_variant | 1/4 | ENST00000262158.8 | |
SMAD7 | NM_001190821.2 | c.254C>T | p.Ala85Val | missense_variant | 1/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SMAD7 | ENST00000262158.8 | c.254C>T | p.Ala85Val | missense_variant | 1/4 | 1 | NM_005904.4 | P4 | |
SMAD7 | ENST00000589634.1 | c.254C>T | p.Ala85Val | missense_variant | 1/4 | 4 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 151918Hom.: 0 Cov.: 32
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1333500Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 657316
GnomAD4 genome ? AF: 0.00000658 AC: 1AN: 151918Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74222
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 02, 2021 | The c.254C>T (p.A85V) alteration is located in exon 1 (coding exon 1) of the SMAD7 gene. This alteration results from a C to T substitution at nucleotide position 254, causing the alanine (A) at amino acid position 85 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