20-2380976-G-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 6P and 6B. PVS1_ModeratePP3_StrongBP6_ModerateBS2
The NM_198994.3(TGM6):c.7+1G>T variant causes a splice donor change. The variant allele was found at a frequency of 0.0000292 in 1,608,644 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000030 ( 0 hom. )
Consequence
TGM6
NM_198994.3 splice_donor
NM_198994.3 splice_donor
Scores
2
3
2
Splicing: ADA: 1.000
2
Clinical Significance
Conservation
PhyloP100: 3.80
Genes affected
TGM6 (HGNC:16255): (transglutaminase 6) The protein encoded by this gene belongs to the transglutaminase superfamily. It catalyzes the cross-linking of proteins and the conjugation of polyamines to proteins. Mutations in this gene are associated with spinocerebellar ataxia type 35 (SCA35). Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PVS1
?
Splicing variant, NOT destroyed by nmd, known LOF gene, truncates exone, which is 0.034889203 fraction of the gene. No cryptic splice site detected. Exon removal is inframe change.
PP3
?
Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF, max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.
BP6
?
Variant 20-2380976-G-T is Benign according to our data. Variant chr20-2380976-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 2152324.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
?
High AC in GnomAdExome at 34 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TGM6 | NM_198994.3 | c.7+1G>T | splice_donor_variant | ENST00000202625.7 | |||
TGM6 | NM_001254734.2 | c.7+1G>T | splice_donor_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TGM6 | ENST00000202625.7 | c.7+1G>T | splice_donor_variant | 1 | NM_198994.3 | P1 | |||
TGM6 | ENST00000381423.1 | c.7+1G>T | splice_donor_variant | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152178Hom.: 0 Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.000142 AC: 34AN: 239268Hom.: 0 AF XY: 0.000132 AC XY: 17AN XY: 129044
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GnomAD4 exome AF: 0.0000295 AC: 43AN: 1456466Hom.: 0 Cov.: 32 AF XY: 0.0000304 AC XY: 22AN XY: 723758
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GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152178Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74346
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2023 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
Cadd
Pathogenic
Dann
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
MutationTaster
Benign
D;D
GERP RS
Splicing
Name
Calibrated prediction
Score
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dbscSNV1_ADA
Pathogenic
dbscSNV1_RF
Pathogenic
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_DG_spliceai
Position offset: -2
DS_DL_spliceai
Position offset: -1
Find out detailed SpliceAI scores and Pangolin per-transcript scores at