20-2381278-A-G

Variant names:

• chr20-2381278-A-G
• rs2422754
• NM_198994.3:c.7+303A>G

Variant summary

Our verdict is Benign. The variant received -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
• 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 35

  Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE, LIMITED Submitted by: PanelApp Australia, Orphanet, Ambry Genetics, Illumina, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198994.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TGM6	NM_198994.3	MANE Select	c.7+303A>G		intron	N/A	NP_945345.2	O95932-1
	TGM6	NM_001254734.2		c.7+303A>G		intron	N/A	NP_001241663.1	O95932-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TGM6	ENST00000202625.7	TSL:1 MANE Select	c.7+303A>G		intron	N/A	ENSP00000202625.2	O95932-1
	TGM6	ENST00000381423.1	TSL:1	c.7+303A>G		intron	N/A	ENSP00000370831.1	O95932-2

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

African (AFR) AF: 0.924 AC: 38349 AN: 41516

American (AMR) AF: 0.709 AC: 10839 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.747 AC: 2591 AN: 3470

East Asian (EAS) AF: 0.485 AC: 2496 AN: 5148

South Asian (SAS) AF: 0.545 AC: 2622 AN: 4814

European-Finnish (FIN) AF: 0.779 AC: 8244 AN: 10578

Middle Eastern (MID) AF: 0.718 AC: 211 AN: 294

European-Non Finnish (NFE) AF: 0.754 AC: 51278 AN: 67984

Other (OTH) AF: 0.755 AC: 1592 AN: 2108

Alfa AF: 0.782 Hom.: 6071

Bravo AF: 0.784

Asia WGS AF: 0.559 AC: 1944 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.1
DANN	Benign	0.29
PhyloP100		-0.71
PromoterAI		-0.016	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2422754; hg19: chr20-2361924;