rs876657385
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_153816.6(SNX14):c.2596C>T(p.Gln866Ter) variant causes a stop gained change. The variant allele was found at a frequency of 0.00000205 in 1,460,550 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 Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000021 ( 0 hom. )
Consequence
SNX14
NM_153816.6 stop_gained
NM_153816.6 stop_gained
Scores
4
2
1
Clinical Significance
Conservation
PhyloP100: 4.08
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 Pathogenic. Variant got 11 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 6-85513857-G-A is Pathogenic according to our data. Variant chr6-85513857-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 190314.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr6-85513857-G-A is described in Lovd as [Likely_pathogenic]. Variant chr6-85513857-G-A is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SNX14 | NM_153816.6 | c.2596C>T | p.Gln866Ter | stop_gained | 26/29 | ENST00000314673.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SNX14 | ENST00000314673.8 | c.2596C>T | p.Gln866Ter | stop_gained | 26/29 | 1 | NM_153816.6 | P4 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1460550Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1AN XY: 726604
GnomAD4 exome
AF:
AC:
3
AN:
1460550
Hom.:
Cov.:
30
AF XY:
AC XY:
1
AN XY:
726604
Gnomad4 AFR exome
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GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Autosomal recessive spinocerebellar ataxia 20 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Nov 06, 2014 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
MutationTaster
Benign
A;A;A;A;A
Vest4
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AL_spliceai
Position offset: 38
Find out detailed SpliceAI scores and Pangolin per-transcript scores at