20-2381132-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_198994.3(TGM6):c.7+157G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0197 in 152,246 control chromosomes in the GnomAD database, including 42 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.020 (42 hom., cov: 32)
• Consequence: TGM6 NM_198994.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.818

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=-0.86).
• BP6: Variant 20-2381132-G-T is Benign according to our data. Variant chr20-2381132-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 1326244.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0197 (2994/152246) while in subpopulation AMR AF= 0.0327 (501/15298). AF 95% confidence interval is 0.0304. There are 42 homozygotes in gnomad4. There are 1473 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd at 2994 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TGM6	NM_198994.3	c.7+157G>T		intron_variant		ENST00000202625.7
TGM6	NM_001254734.2	c.7+157G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TGM6	ENST00000202625.7	c.7+157G>T		intron_variant		1	NM_198994.3	P1
TGM6	ENST00000381423.1	c.7+157G>T		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.0197 AC: 2994 AN: 152128 Hom.: 42 Cov.: 32

Gnomad AFR AF: 0.0202

Gnomad AMI AF: 0.0186

Gnomad AMR AF: 0.0327

Gnomad ASJ AF: 0.0323

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00228

Gnomad FIN AF: 0.0208

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0180

Gnomad OTH AF: 0.0234

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

GnomAD4 genome AF: 0.0197 AC: 2994 AN: 152246 Hom.: 42 Cov.: 32 AF XY: 0.0198 AC XY: 1473 AN XY: 74432

Gnomad4 AFR AF: 0.0202

Gnomad4 AMR AF: 0.0327

Gnomad4 ASJ AF: 0.0323

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00207

Gnomad4 FIN AF: 0.0208

Gnomad4 NFE AF: 0.0180

Gnomad4 OTH AF: 0.0232

Alfa AF: 0.00763 Hom.: 2

Bravo AF: 0.0219

Asia WGS AF: 0.00346 AC: 12 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

May 19, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	1.8
Dann	Benign	0.79

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: rs17222895; hg19: chr20-2361778;