13-36867298-A-G
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_001127217.3(SMAD9):c.756T>C(p.His252His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0043 in 1,550,138 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_001127217.3 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -21 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SMAD9 | ENST00000379826.5 | c.756T>C | p.His252His | synonymous_variant | Exon 4 of 7 | 5 | NM_001127217.3 | ENSP00000369154.4 | ||
SMAD9 | ENST00000350148.10 | c.671-1540T>C | intron_variant | Intron 3 of 5 | 1 | ENSP00000239885.6 | ||||
SMAD9 | ENST00000399275.7 | n.*381-1540T>C | intron_variant | Intron 3 of 5 | 1 | ENSP00000382216.3 |
Frequencies
GnomAD3 genomes AF: 0.00361 AC: 550AN: 152166Hom.: 1 Cov.: 32
GnomAD3 exomes AF: 0.00364 AC: 569AN: 156490Hom.: 3 AF XY: 0.00333 AC XY: 276AN XY: 82946
GnomAD4 exome AF: 0.00437 AC: 6113AN: 1397854Hom.: 21 Cov.: 29 AF XY: 0.00432 AC XY: 2977AN XY: 689490
GnomAD4 genome AF: 0.00361 AC: 550AN: 152284Hom.: 1 Cov.: 32 AF XY: 0.00329 AC XY: 245AN XY: 74458
ClinVar
Submissions by phenotype
not provided Benign:3
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SMAD9: BP4, BP7, BS2 -
Pulmonary hypertension, primary, 2 Benign:2
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not specified Benign:1
p.His252His in exon 4 of SMAD9: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue and is not located wi thin the splice consensus sequence. It has been identified in 0.6% (49/8748) of European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broa dinstitute.org; dbSNP rs146836873). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at