15-66703988-C-T
Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_005585.5(SMAD6):c.730C>T(p.Leu244=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000877 in 1,482,914 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 Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. L244L) has been classified as Likely benign.
Frequency
Consequence
NM_005585.5 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -17 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SMAD6 | NM_005585.5 | c.730C>T | p.Leu244= | synonymous_variant | 1/4 | ENST00000288840.10 | |
SMAD6 | NR_027654.2 | n.1753C>T | non_coding_transcript_exon_variant | 1/5 | |||
SMAD6 | XR_931827.3 | n.1753C>T | non_coding_transcript_exon_variant | 1/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SMAD6 | ENST00000288840.10 | c.730C>T | p.Leu244= | synonymous_variant | 1/4 | 1 | NM_005585.5 | P1 | |
SMAD6 | ENST00000557916.5 | c.730C>T | p.Leu244= | synonymous_variant, NMD_transcript_variant | 1/5 | 1 | |||
SMAD6 | ENST00000612349.1 | n.912C>T | non_coding_transcript_exon_variant | 1/1 |
Frequencies
GnomAD3 genomes AF: 0.0000132 AC: 2AN: 152046Hom.: 0 Cov.: 33
GnomAD4 exome AF: 0.00000827 AC: 11AN: 1330868Hom.: 0 Cov.: 32 AF XY: 0.00000456 AC XY: 3AN XY: 657670
GnomAD4 genome AF: 0.0000132 AC: 2AN: 152046Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74278
ClinVar
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Aug 10, 2023 | - - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 06, 2019 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Aortic valve disease 2 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jun 22, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at