rs779514800
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_001242957.3(MAK):c.718C>T(p.Gln240*) variant causes a stop gained change. The variant allele was found at a frequency of 0.00000205 in 1,461,814 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: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )
Consequence
MAK
NM_001242957.3 stop_gained
NM_001242957.3 stop_gained
Scores
4
2
1
Clinical Significance
Conservation
PhyloP100: 5.30
Genes affected
MAK (HGNC:6816): (male germ cell associated kinase) The product of this gene is a serine/threonine protein kinase related to kinases involved in cell cycle regulation. Studies of the mouse and rat homologs have localized the kinase to the chromosomes during meiosis in spermatogenesis, specifically to the synaptonemal complex that exists while homologous chromosomes are paired. Mutations in this gene have been associated with ciliary defects resulting in retinitis pigmentosa 62. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]
TMEM14B (HGNC:21384): (transmembrane protein 14B) Enables identical protein binding activity. Involved in cerebral cortex development; neural precursor cell proliferation; and regulation of G1/S transition of mitotic cell cycle. Predicted to be integral component of membrane. Predicted to be active in mitochondrial inner membrane. [provided by Alliance of Genome Resources, Apr 2022]
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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 6-10802005-G-A is Pathogenic according to our data. Variant chr6-10802005-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 29781.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr6-10802005-G-A is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461814Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 727218
GnomAD4 exome
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3
AN:
1461814
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Cov.:
32
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1
AN XY:
727218
Gnomad4 AFR exome
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GnomAD4 genome
GnomAD4 genome
Cov.:
32
TwinsUK
AF:
AC:
0
ALSPAC
AF:
AC:
1
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Retinitis pigmentosa 62 Pathogenic:1
Aug 12, 2011
OMIM
Significance: Pathogenic
Review Status: no assertion criteria provided
Collection Method: literature only
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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
Vest4
GERP RS
Splicing
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Calibrated prediction
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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