NM_198994.3:c.1668G>T
Variant names:
Variant summary
Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_Very_StrongBP7BS2_Supporting
The NM_198994.3(TGM6):c.1668G>T(p.Gly556Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000131 in 1,600,824 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 0.000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000076 ( 0 hom. )
Consequence
TGM6
NM_198994.3 synonymous
NM_198994.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.304
Publications
0 publications found
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]
TGM6 Gene-Disease associations (from GenCC):
- spinocerebellar ataxia type 35Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, Illumina, Labcorp Genetics (formerly Invitae), Orphanet
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Benign. The variant received -14 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BP6
Variant 20-2417563-G-T is Benign according to our data. Variant chr20-2417563-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 586818.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-0.304 with no splicing effect.
BS2
High AC in GnomAd4 at 10 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TGM6 | ENST00000202625.7 | c.1668G>T | p.Gly556Gly | synonymous_variant | Exon 10 of 13 | 1 | NM_198994.3 | ENSP00000202625.2 | ||
TGM6 | ENST00000381423.1 | c.1668G>T | p.Gly556Gly | synonymous_variant | Exon 10 of 12 | 1 | ENSP00000370831.1 |
Frequencies
GnomAD3 genomes AF: 0.0000657 AC: 10AN: 152188Hom.: 0 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
10
AN:
152188
Hom.:
Cov.:
32
Gnomad AFR
AF:
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Gnomad OTH
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GnomAD2 exomes AF: 0.0000214 AC: 5AN: 233956 AF XY: 0.00000782 show subpopulations
GnomAD2 exomes
AF:
AC:
5
AN:
233956
AF XY:
Gnomad AFR exome
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GnomAD4 exome AF: 0.00000759 AC: 11AN: 1448636Hom.: 0 Cov.: 33 AF XY: 0.00000555 AC XY: 4AN XY: 720892 show subpopulations
GnomAD4 exome
AF:
AC:
11
AN:
1448636
Hom.:
Cov.:
33
AF XY:
AC XY:
4
AN XY:
720892
show subpopulations
African (AFR)
AF:
AC:
10
AN:
33412
American (AMR)
AF:
AC:
1
AN:
44574
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26062
East Asian (EAS)
AF:
AC:
0
AN:
39650
South Asian (SAS)
AF:
AC:
0
AN:
85938
European-Finnish (FIN)
AF:
AC:
0
AN:
41550
Middle Eastern (MID)
AF:
AC:
0
AN:
5696
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1111490
Other (OTH)
AF:
AC:
0
AN:
60264
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.470
Heterozygous variant carriers
0
1
3
4
6
7
0.00
0.20
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0.60
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0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
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Age
GnomAD4 genome AF: 0.0000657 AC: 10AN: 152188Hom.: 0 Cov.: 32 AF XY: 0.0000673 AC XY: 5AN XY: 74334 show subpopulations
GnomAD4 genome
AF:
AC:
10
AN:
152188
Hom.:
Cov.:
32
AF XY:
AC XY:
5
AN XY:
74334
show subpopulations
African (AFR)
AF:
AC:
9
AN:
41456
American (AMR)
AF:
AC:
1
AN:
15284
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3472
East Asian (EAS)
AF:
AC:
0
AN:
5176
South Asian (SAS)
AF:
AC:
0
AN:
4830
European-Finnish (FIN)
AF:
AC:
0
AN:
10618
Middle Eastern (MID)
AF:
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
AC:
0
AN:
68036
Other (OTH)
AF:
AC:
0
AN:
2088
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.500
Heterozygous variant carriers
0
1
2
2
3
4
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Genome Het
Variant carriers
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Age
Alfa
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Bravo
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Mar 24, 2021
Athena Diagnostics
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
not provided Benign:1
Aug 01, 2023
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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