chr4-950422-A-C
Variant names:
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 2P and 16B. PVS1_ModerateBP6_Very_StrongBA1
The NM_001297425.2(TMEM175):c.-51-2A>C variant causes a splice acceptor, intron change. The variant allele was found at a frequency of 0.0918 in 1,611,220 control chromosomes in the GnomAD database, including 7,834 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.068 ( 516 hom., cov: 32)
Exomes 𝑓: 0.094 ( 7318 hom. )
Consequence
TMEM175
NM_001297425.2 splice_acceptor, intron
NM_001297425.2 splice_acceptor, intron
Scores
1
7
Splicing: ADA: 0.00001931
2
Clinical Significance
Conservation
PhyloP100: 3.96
Genes affected
TMEM175 (HGNC:28709): (transmembrane protein 175) Enables potassium ion leak channel activity. Involved in potassium ion transmembrane transport. Located in endosome and lysosome. Is integral component of endosome membrane and integral component of lysosomal membrane. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
PVS1
Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.07486209 fraction of the gene. Cryptic splice site detected, with MaxEntScore 6, offset of -3, new splice context is: gcagtgctcttgtattccAGccg. Cryptic site results in inframe change. If cryptic site found is not functional and variant results in exon loss, it results in frameshift change.
BP6
Variant 4-950422-A-C is Benign according to our data. Variant chr4-950422-A-C is described in ClinVar as [Benign]. Clinvar id is 1178472.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.104 is higher than 0.05.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0679 AC: 10336AN: 152196Hom.: 516 Cov.: 32
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GnomAD3 exomes AF: 0.0703 AC: 17645AN: 251040Hom.: 891 AF XY: 0.0714 AC XY: 9684AN XY: 135698
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GnomAD4 exome AF: 0.0943 AC: 137619AN: 1458906Hom.: 7318 Cov.: 30 AF XY: 0.0927 AC XY: 67282AN XY: 726034
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GnomAD4 genome AF: 0.0679 AC: 10336AN: 152314Hom.: 516 Cov.: 32 AF XY: 0.0644 AC XY: 4797AN XY: 74484
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376
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438
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101
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 19, 2019 | This variant is associated with the following publications: (PMID: 31658403, 30389748) - |
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at