rs10485600

chr20-2419857-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_198994.3(TGM6):c.1678+2284C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 152,236 control chromosomes in the GnomAD database, including 828 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.11 (828 hom., cov: 32)
• Consequence: TGM6 NM_198994.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.305

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.135 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TGM6	NM_198994.3	c.1678+2284C>A		intron_variant		ENST00000202625.7
TGM6	NM_001254734.2	c.1678+2284C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TGM6	ENST00000202625.7	c.1678+2284C>A		intron_variant		1	NM_198994.3	P1
TGM6	ENST00000381423.1	c.1678+2284C>A		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.105 AC: 15985 AN: 152118 Hom.: 827 Cov.: 32

Gnomad AFR AF: 0.118

Gnomad AMI AF: 0.0417

Gnomad AMR AF: 0.0852

Gnomad ASJ AF: 0.0772

Gnomad EAS AF: 0.144

Gnomad SAS AF: 0.144

Gnomad FIN AF: 0.0975

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0998

Gnomad OTH AF: 0.104

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

GnomAD4 genome AF: 0.105 AC: 15993 AN: 152236 Hom.: 828 Cov.: 32 AF XY: 0.106 AC XY: 7874 AN XY: 74422

Gnomad4 AFR AF: 0.118

Gnomad4 AMR AF: 0.0851

Gnomad4 ASJ AF: 0.0772

Gnomad4 EAS AF: 0.143

Gnomad4 SAS AF: 0.144

Gnomad4 FIN AF: 0.0975

Gnomad4 NFE AF: 0.0998

Gnomad4 OTH AF: 0.103

Alfa AF: 0.104 Hom.: 461

Bravo AF: 0.106

Asia WGS AF: 0.141 AC: 493 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	1.1
Dann	Benign	0.74

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: rs10485600; hg19: chr20-2400503;