rs756752655
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBS1_SupportingBS2
The NM_005585.5(SMAD6):āc.173C>Gā(p.Ser58Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00021 in 1,292,696 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S58P) has been classified as Uncertain significance.
Frequency
Consequence
NM_005585.5 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Benign. Variant got -7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SMAD6 | NM_005585.5 | c.173C>G | p.Ser58Cys | missense_variant | 1/4 | ENST00000288840.10 | |
SMAD6 | NR_027654.2 | n.1196C>G | non_coding_transcript_exon_variant | 1/5 | |||
SMAD6 | XR_931827.3 | n.1196C>G | non_coding_transcript_exon_variant | 1/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SMAD6 | ENST00000288840.10 | c.173C>G | p.Ser58Cys | missense_variant | 1/4 | 1 | NM_005585.5 | P1 | |
SMAD6 | ENST00000557916.5 | c.173C>G | p.Ser58Cys | missense_variant, NMD_transcript_variant | 1/5 | 1 | |||
SMAD6 | ENST00000612349.1 | n.355C>G | non_coding_transcript_exon_variant | 1/1 |
Frequencies
GnomAD3 genomes ? AF: 0.000237 AC: 36AN: 151654Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000388 AC: 5AN: 12886Hom.: 0 AF XY: 0.000311 AC XY: 2AN XY: 6426
GnomAD4 exome AF: 0.000206 AC: 235AN: 1141042Hom.: 1 Cov.: 32 AF XY: 0.000212 AC XY: 116AN XY: 547286
GnomAD4 genome ? AF: 0.000237 AC: 36AN: 151654Hom.: 0 Cov.: 33 AF XY: 0.000148 AC XY: 11AN XY: 74076
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 24, 2024 | The c.173C>G (p.S58C) alteration is located in exon 1 (coding exon 1) of the SMAD6 gene. This alteration results from a C to G substitution at nucleotide position 173, causing the serine (S) at amino acid position 58 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Aortic valve disease 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 01, 2022 | This sequence change replaces serine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 58 of the SMAD6 protein (p.Ser58Cys). This variant is present in population databases (rs756752655, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with SMAD6-related conditions. ClinVar contains an entry for this variant (Variation ID: 571213). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at