rs143946794
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_001946.4(DUSP6):āc.566A>Gā(p.Asn189Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000237 in 1,614,050 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Consequence
NM_001946.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DUSP6 | NM_001946.4 | c.566A>G | p.Asn189Ser | missense_variant | 2/3 | ENST00000279488.8 | |
DUSP6 | NM_022652.4 | c.400+780A>G | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DUSP6 | ENST00000279488.8 | c.566A>G | p.Asn189Ser | missense_variant | 2/3 | 1 | NM_001946.4 | P1 | |
DUSP6 | ENST00000308385.6 | c.400+780A>G | intron_variant | 1 | |||||
DUSP6 | ENST00000547291.1 | c.191A>G | p.Asn64Ser | missense_variant | 1/2 | 2 | |||
DUSP6 | ENST00000547140.1 | n.252A>G | non_coding_transcript_exon_variant | 2/3 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.000191 AC: 29AN: 152106Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000195 AC: 49AN: 251356Hom.: 0 AF XY: 0.000213 AC XY: 29AN XY: 135862
GnomAD4 exome AF: 0.000242 AC: 354AN: 1461826Hom.: 1 Cov.: 30 AF XY: 0.000256 AC XY: 186AN XY: 727210
GnomAD4 genome ? AF: 0.000191 AC: 29AN: 152224Hom.: 0 Cov.: 32 AF XY: 0.000188 AC XY: 14AN XY: 74432
ClinVar
Submissions by phenotype
Hypogonadotropic hypogonadism 19 with or without anosmia Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | May 02, 2013 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 06, 2022 | This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 189 of the DUSP6 protein (p.Asn189Ser). This variant is present in population databases (rs143946794, gnomAD 0.04%). This missense change has been observed in individual(s) with Kallman syndrome (PMID: 23643382). ClinVar contains an entry for this variant (Variation ID: 50854). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The serine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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