chr20-2381148-G-A

Position:

• chr20-2381148-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_198994.3(TGM6):​c.7+173G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.085 in 152,230 control chromosomes in the GnomAD database, including 641 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.085 (641 hom., cov: 32)
• Consequence: TGM6 NM_198994.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.506

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 20-2381148-G-A is Benign according to our data. Variant chr20-2381148-G-A is described in ClinVar as [Benign]. Clinvar id is 1295584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.109 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TGM6	NM_198994.3	c.7+173G>A		intron_variant		ENST00000202625.7
TGM6	NM_001254734.2	c.7+173G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TGM6	ENST00000202625.7	c.7+173G>A		intron_variant		1	NM_198994.3	P1
TGM6	ENST00000381423.1	c.7+173G>A		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.0849 AC: 12915 AN: 152112 Hom.: 640 Cov.: 32

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.0570

Gnomad ASJ AF: 0.0268

Gnomad EAS AF: 0.0303

Gnomad SAS AF: 0.0217

Gnomad FIN AF: 0.151

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0780

Gnomad OTH AF: 0.0737

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

GnomAD4 genome AF: 0.0850 AC: 12942 AN: 152230 Hom.: 641 Cov.: 32 AF XY: 0.0861 AC XY: 6406 AN XY: 74422

Gnomad4 AFR AF: 0.111

Gnomad4 AMR AF: 0.0570

Gnomad4 ASJ AF: 0.0268

Gnomad4 EAS AF: 0.0303

Gnomad4 SAS AF: 0.0220

Gnomad4 FIN AF: 0.151

Gnomad4 NFE AF: 0.0780

Gnomad4 OTH AF: 0.0734

Alfa AF: 0.0856 Hom.: 95

Bravo AF: 0.0811

Asia WGS AF: 0.0340 AC: 119 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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	May 15, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.78
DANN	Benign	0.62

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: rs16984767; hg19: chr20-2361794;