rs61753157
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_001127217.3(SMAD9):c.487G>A(p.Ala163Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00254 in 1,613,992 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_001127217.3 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SMAD9 | NM_001127217.3 | c.487G>A | p.Ala163Thr | missense_variant | 3/7 | ENST00000379826.5 | NP_001120689.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SMAD9 | ENST00000379826.5 | c.487G>A | p.Ala163Thr | missense_variant | 3/7 | 5 | NM_001127217.3 | ENSP00000369154 | P1 | |
SMAD9 | ENST00000350148.10 | c.487G>A | p.Ala163Thr | missense_variant | 3/6 | 1 | ENSP00000239885 | |||
SMAD9 | ENST00000399275.7 | c.*197G>A | 3_prime_UTR_variant, NMD_transcript_variant | 3/6 | 1 | ENSP00000382216 |
Frequencies
GnomAD3 genomes AF: 0.00143 AC: 218AN: 151996Hom.: 1 Cov.: 31
GnomAD3 exomes AF: 0.00115 AC: 289AN: 251236Hom.: 0 AF XY: 0.00113 AC XY: 153AN XY: 135796
GnomAD4 exome AF: 0.00265 AC: 3877AN: 1461878Hom.: 6 Cov.: 33 AF XY: 0.00253 AC XY: 1840AN XY: 727240
GnomAD4 genome AF: 0.00143 AC: 218AN: 152114Hom.: 1 Cov.: 31 AF XY: 0.00112 AC XY: 83AN XY: 74364
ClinVar
Submissions by phenotype
not specified Benign:3
Likely benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jan 16, 2018 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 24, 2013 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Sep 30, 2015 | p.Ala163Thr in exon 3 of SMAD9: This variant is not expected to have clinical si gnificance because it has been identified in 0.2% (116/66698) of European chromo somes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs61753157). - |
Pulmonary hypertension, primary, 2 Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 28, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Mar 20, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at