rs748847284
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Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_001201543.2(FAM161A):c.847C>T(p.Arg283*) variant causes a stop gained change. The variant allele was found at a frequency of 0.0000149 in 1,614,058 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 Likely pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000015 ( 0 hom. )
Consequence
FAM161A
NM_001201543.2 stop_gained
NM_001201543.2 stop_gained
Scores
5
1
1
Clinical Significance
Conservation
PhyloP100: 5.10
Genes affected
FAM161A (HGNC:25808): (FAM161 centrosomal protein A) This gene belongs to the FAM161 family. It is expressed mainly in the retina. Mouse studies suggested that this gene is involved in development of retinal progenitors during embryogenesis, and that its activity is restricted to mature photoreceptors after birth. Mutations in this gene cause autosomal recessive retinitis pigmentosa-28. Alternatively spliced transcript variants have been identified.[provided by RefSeq, Jan 2011]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 18 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 2-61840157-G-A is Pathogenic according to our data. Variant chr2-61840157-G-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 546864.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-61840157-G-A is described in Lovd as [Likely_pathogenic].
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000132 AC: 2AN: 152070Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000241 AC: 6AN: 249180Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135198
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GnomAD4 exome AF: 0.0000150 AC: 22AN: 1461870Hom.: 0 Cov.: 36 AF XY: 0.0000165 AC XY: 12AN XY: 727234
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GnomAD4 genome AF: 0.0000131 AC: 2AN: 152188Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74414
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ClinVar
Significance: Pathogenic/Likely pathogenic
Submissions summary: Pathogenic:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Retinitis pigmentosa 28 Pathogenic:3
Likely pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Feb 08, 2024 | - - |
Likely pathogenic, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Jul 20, 2021 | - - |
Likely pathogenic, criteria provided, single submitter | clinical testing | Molecular Diagnostics Laboratory, M Health Fairview: University of Minnesota | Nov 27, 2017 | - - |
not provided Pathogenic:2
Likely pathogenic, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jul 01, 2018 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Nov 27, 2023 | This sequence change creates a premature translational stop signal (p.Arg283*) in the FAM161A gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in FAM161A are known to be pathogenic (PMID: 20705278, 20705279, 24651477). This variant is present in population databases (rs748847284, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with FAM161A-related conditions. ClinVar contains an entry for this variant (Variation ID: 546864). For these reasons, this variant has been classified as Pathogenic. - |
Retinitis pigmentosa Pathogenic:1
Pathogenic, criteria provided, single submitter | research | Molecular Genetics Laboratory, Institute for Ophthalmic Research | Jan 09, 2020 | - - |
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
Pathogenic
D
Vest4
GERP RS
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