20-2381278-A-G

Position:

• chr20-2381278-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_198994.3(TGM6):​c.7+303A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.782 in 152,110 control chromosomes in the GnomAD database, including 47,404 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.78 (47404 hom., cov: 30)
• Consequence: TGM6 NM_198994.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.711

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 20-2381278-A-G is Benign according to our data. Variant chr20-2381278-A-G is described in ClinVar as [Benign]. Clinvar id is 1245437.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.916 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TGM6	NM_198994.3	c.7+303A>G		intron_variant		ENST00000202625.7
TGM6	NM_001254734.2	c.7+303A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TGM6	ENST00000202625.7	c.7+303A>G		intron_variant		1	NM_198994.3	P1
TGM6	ENST00000381423.1	c.7+303A>G		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.782 AC: 118801 AN: 151992 Hom.: 47358 Cov.: 30

Gnomad AFR AF: 0.924

Gnomad AMI AF: 0.744

Gnomad AMR AF: 0.709

Gnomad ASJ AF: 0.747

Gnomad EAS AF: 0.485

Gnomad SAS AF: 0.545

Gnomad FIN AF: 0.779

Gnomad MID AF: 0.715

Gnomad NFE AF: 0.754

Gnomad OTH AF: 0.759

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.782 AC: 118899 AN: 152110 Hom.: 47404 Cov.: 30 AF XY: 0.775 AC XY: 57599 AN XY: 74350

Gnomad4 AFR AF: 0.924

Gnomad4 AMR AF: 0.709

Gnomad4 ASJ AF: 0.747

Gnomad4 EAS AF: 0.485

Gnomad4 SAS AF: 0.545

Gnomad4 FIN AF: 0.779

Gnomad4 NFE AF: 0.754

Gnomad4 OTH AF: 0.755

Alfa AF: 0.776 Hom.: 5729

Bravo AF: 0.784

Asia WGS AF: 0.559 AC: 1944 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

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	-0.92
CADD	Benign	1.1
DANN	Benign	0.29

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

Other links and lift over

dbSNP: rs2422754; hg19: chr20-2361924;