chr6-85505953-C-A
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBS1_Supporting
The NM_153816.6(SNX14):c.*14G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000165 in 1,593,860 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 Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00091 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000087 ( 1 hom. )
Consequence
SNX14
NM_153816.6 3_prime_UTR
NM_153816.6 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.792
Genes affected
SNX14 (HGNC:14977): (sorting nexin 14) This gene encodes a member of the sorting nexin family. Members of this family have a phox (PX) phosphoinositide binding domain and are involved in intracellular trafficking. The encoded protein also contains a regulator of G protein signaling (RGS) domain. Regulator of G protein signaling family members are regulatory molecules that act as GTPase activating proteins for G alpha subunits of heterotrimeric G proteins. Alternate splicing results in transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2014]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -3 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.74).
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000906 (138/152258) while in subpopulation AFR AF= 0.0033 (137/41570). AF 95% confidence interval is 0.00285. There are 0 homozygotes in gnomad4. There are 64 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SNX14 | NM_153816.6 | c.*14G>T | 3_prime_UTR_variant | 29/29 | ENST00000314673.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SNX14 | ENST00000314673.8 | c.*14G>T | 3_prime_UTR_variant | 29/29 | 1 | NM_153816.6 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.000907 AC: 138AN: 152140Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000176 AC: 44AN: 250450Hom.: 0 AF XY: 0.000133 AC XY: 18AN XY: 135424
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GnomAD4 exome AF: 0.0000867 AC: 125AN: 1441602Hom.: 1 Cov.: 26 AF XY: 0.0000710 AC XY: 51AN XY: 718624
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Aug 24, 2023 | Variant summary: SNX14 c.*14G>T is located in the 3' untranslated mRNA region downstream of the termination codon. The variant allele was found at a frequency of 0.00018 in 250450 control chromosomes, predominantly at a frequency of 0.0027 within the African or African-American subpopulation in the gnomAD database. To our knowledge, no occurrence of c.*14G>T in individuals affected with Autosomal Recessive Spinocerebellar Ataxia and no experimental evidence demonstrating its impact on protein function have been reported. No submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance. - |
Computational scores
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Name
Calibrated prediction
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at