chr20-2381021-G-A

Position:

• chr20-2381021-G-A

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+46G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00138 in 1,605,530 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0067 (14 hom., cov: 32)
  • Exomes 𝑓: 0.00082 (7 hom.)
• Consequence: TGM6 NM_198994.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.773

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=-0.97).
• BP6: Variant 20-2381021-G-A is Benign according to our data. Variant chr20-2381021-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1698253.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00673 (1025/152274) while in subpopulation AFR AF= 0.0231 (962/41558). AF 95% confidence interval is 0.0219. There are 14 homozygotes in gnomad4. There are 482 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1025 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TGM6	NM_198994.3	c.7+46G>A		intron_variant		ENST00000202625.7
TGM6	NM_001254734.2	c.7+46G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TGM6	ENST00000202625.7	c.7+46G>A		intron_variant		1	NM_198994.3	P1
TGM6	ENST00000381423.1	c.7+46G>A		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.00671 AC: 1021 AN: 152156 Hom.: 14 Cov.: 32

Gnomad AFR AF: 0.0231

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00236

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00814

GnomAD3 exomes AF: 0.00179 AC: 414 AN: 230908 Hom.: 3 AF XY: 0.00128 AC XY: 159 AN XY: 124192

Gnomad AFR exome AF: 0.0241

Gnomad AMR exome AF: 0.000899

Gnomad ASJ exome AF: 0.00137

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000363

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000957

Gnomad OTH exome AF: 0.00142

GnomAD4 exome AF: 0.000821 AC: 1193 AN: 1453256 Hom.: 7 Cov.: 32 AF XY: 0.000718 AC XY: 518 AN XY: 721732

Gnomad4 AFR exome AF: 0.0270

Gnomad4 AMR exome AF: 0.000904

Gnomad4 ASJ exome AF: 0.00155

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000836

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000496

Gnomad4 OTH exome AF: 0.00220

GnomAD4 genome AF: 0.00673 AC: 1025 AN: 152274 Hom.: 14 Cov.: 32 AF XY: 0.00647 AC XY: 482 AN XY: 74462

Gnomad4 AFR AF: 0.0231

Gnomad4 AMR AF: 0.00235

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000882

Gnomad4 OTH AF: 0.00806

Alfa AF: 0.00372 Hom.: 1

Bravo AF: 0.00835

Asia WGS AF: 0.00260 AC: 9 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

Jan 19, 2022

See Variant Classification Assertion Criteria. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.24
DANN	Benign	0.61

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: rs151031920; hg19: chr20-2361667;