Variant 20-2381038-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_198994.3(TGM6):c.7+63C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.738 in 1,593,926 control chromosomes in the GnomAD database, including 439,418 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.77 ( 46342 hom., cov: 31)

Exomes 𝑓: 0.73 ( 393076 hom. )

Consequence

TGM6
NM_198994.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.69

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 20-2381038-C-T is Benign according to our data. Variant chr20-2381038-C-T is described in ClinVar as [Benign]. Clinvar id is 1234125.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.891 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TGM6	NM_198994.3 link	c.7+63C>T		intron_variant		ENST00000202625.7	NP_945345.2	O95932-1
TGM6	NM_001254734.2 link	c.7+63C>T		intron_variant			NP_001241663.1	O95932-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TGM6	ENST00000202625.7 link	c.7+63C>T		intron_variant		1	NM_198994.3	ENSP00000202625.2		O95932-1
TGM6	ENST00000381423.1 link	c.7+63C>T		intron_variant		1		ENSP00000370831.1		O95932-2

Frequencies

GnomAD3 genomes

AF:

0.774

AC:

117592

AN:

151960

Hom.:

46303

Cov.:

show subpopulations

Gnomad AFR

AF:

0.898

Gnomad AMI

AF:

0.745

Gnomad AMR

AF:

0.707

Gnomad ASJ

AF:

0.745

Gnomad EAS

AF:

0.475

Gnomad SAS

AF:

0.544

Gnomad FIN

AF:

0.778

Gnomad MID

AF:

0.715

Gnomad NFE

AF:

0.754

Gnomad OTH

AF:

0.750

GnomAD4 exome

AF:

0.734

AC:

1058724

AN:

1441850

Hom.:

393076

AF XY:

0.729

AC XY:

521144

AN XY:

715296

show subpopulations

Gnomad4 AFR exome

AF:

0.904

Gnomad4 AMR exome

AF:

0.637

Gnomad4 ASJ exome

AF:

0.749

Gnomad4 EAS exome

AF:

0.470

Gnomad4 SAS exome

AF:

0.556

Gnomad4 FIN exome

AF:

0.776

Gnomad4 NFE exome

AF:

0.754

Gnomad4 OTH exome

AF:

0.727

GnomAD4 genome

AF:

0.774

AC:

117682

AN:

152076

Hom.:

46342

Cov.:

AF XY:

0.767

AC XY:

57034

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.898

Gnomad4 AMR

AF:

0.707

Gnomad4 ASJ

AF:

0.745

Gnomad4 EAS

AF:

0.475

Gnomad4 SAS

AF:

0.543

Gnomad4 FIN

AF:

0.778

Gnomad4 NFE

AF:

0.754

Gnomad4 OTH

AF:

0.746

Alfa

AF:

0.744

Hom.:

20790

Bravo

AF:

0.774

Asia WGS

AF:

0.554

AC:

1927

AN:

3478

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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 13, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

3.2

DANN

Benign

0.73

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over