rs139318648
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS2
The NM_001946.4(DUSP6):c.545C>T(p.Ser182Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000933 in 1,613,908 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001946.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -7 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DUSP6 | ENST00000279488.8 | c.545C>T | p.Ser182Phe | missense_variant | Exon 2 of 3 | 1 | NM_001946.4 | ENSP00000279488.6 | ||
DUSP6 | ENST00000308385.6 | c.400+759C>T | intron_variant | Intron 1 of 1 | 1 | ENSP00000307835.6 | ||||
DUSP6 | ENST00000547291.1 | c.170C>T | p.Ser57Phe | missense_variant | Exon 1 of 2 | 2 | ENSP00000449838.1 | |||
DUSP6 | ENST00000547140.1 | n.231C>T | non_coding_transcript_exon_variant | Exon 2 of 3 | 3 |
Frequencies
GnomAD3 genomes AF: 0.000900 AC: 137AN: 152180Hom.: 1 Cov.: 32
GnomAD3 exomes AF: 0.000605 AC: 152AN: 251220Hom.: 0 AF XY: 0.000641 AC XY: 87AN XY: 135798
GnomAD4 exome AF: 0.000937 AC: 1369AN: 1461728Hom.: 0 Cov.: 30 AF XY: 0.000942 AC XY: 685AN XY: 727152
GnomAD4 genome AF: 0.000900 AC: 137AN: 152180Hom.: 1 Cov.: 32 AF XY: 0.000753 AC XY: 56AN XY: 74340
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:1
DUSP6: BS1 -
This sequence change replaces serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 182 of the DUSP6 protein (p.Ser182Phe). This variant is present in population databases (rs139318648, gnomAD 0.1%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with DUSP6-related conditions. ClinVar contains an entry for this variant (Variation ID: 50855). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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. -
Hypogonadotropic hypogonadism 19 with or without anosmia Other:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at