15-66703262-T-G
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_005585.5(SMAD6):āc.4T>Gā(p.Phe2Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000076 in 1,316,530 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Consequence
NM_005585.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SMAD6 | NM_005585.5 | c.4T>G | p.Phe2Val | missense_variant | 1/4 | ENST00000288840.10 | NP_005576.3 | |
SMAD6 | NR_027654.2 | n.1027T>G | non_coding_transcript_exon_variant | 1/5 | ||||
SMAD6 | XR_931827.3 | n.1027T>G | non_coding_transcript_exon_variant | 1/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SMAD6 | ENST00000288840.10 | c.4T>G | p.Phe2Val | missense_variant | 1/4 | 1 | NM_005585.5 | ENSP00000288840 | P1 | |
SMAD6 | ENST00000557916.5 | c.4T>G | p.Phe2Val | missense_variant, NMD_transcript_variant | 1/5 | 1 | ENSP00000452955 | |||
SMAD6 | ENST00000612349.1 | n.186T>G | non_coding_transcript_exon_variant | 1/1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome AF: 7.60e-7 AC: 1AN: 1316530Hom.: 0 Cov.: 31 AF XY: 0.00000154 AC XY: 1AN XY: 650142
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 17, 2023 | The c.4T>G (p.F2V) alteration is located in exon 1 (coding exon 1) of the SMAD6 gene. This alteration results from a T to G substitution at nucleotide position 4, causing the phenylalanine (F) at amino acid position 2 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
Publications
No publications associated with this variant yet.