rs779951018
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Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2
The NM_198994.3(TGM6):c.2019C>T(p.Thr673=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000062 in 1,613,996 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000066 ( 0 hom. )
Consequence
TGM6
NM_198994.3 synonymous
NM_198994.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.223
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 Benign. Variant got -15 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.36).
BP6
?
Variant 20-2432541-C-T is Benign according to our data. Variant chr20-2432541-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 586820.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-0.223 with no splicing effect.
BS2
?
High AC in GnomAdExome4 at 97 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TGM6 | NM_198994.3 | c.2019C>T | p.Thr673= | synonymous_variant | 13/13 | ENST00000202625.7 | |
TGM6 | NM_001254734.2 | c.*7C>T | 3_prime_UTR_variant | 12/12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TGM6 | ENST00000202625.7 | c.2019C>T | p.Thr673= | synonymous_variant | 13/13 | 1 | NM_198994.3 | P1 | |
TGM6 | ENST00000381423.1 | c.*7C>T | 3_prime_UTR_variant | 12/12 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152108Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251420Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135882
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GnomAD4 exome AF: 0.0000664 AC: 97AN: 1461888Hom.: 0 Cov.: 43 AF XY: 0.0000564 AC XY: 41AN XY: 727244
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GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152108Hom.: 0 Cov.: 31 AF XY: 0.0000269 AC XY: 2AN XY: 74306
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 28, 2022 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Jun 29, 2018 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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