rs10485600

Variant names:

• chr20-2419857-C-A
• rs10485600
• NM_198994.3:c.1678+2284C>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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: Ambry Genetics, Illumina, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TGM6	NM_198994.3	MANE Select	c.1678+2284C>A		intron	N/A	NP_945345.2
	TGM6	NM_001254734.2		c.1678+2284C>A		intron	N/A	NP_001241663.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TGM6	ENST00000202625.7	TSL:1 MANE Select	c.1678+2284C>A		intron	N/A	ENSP00000202625.2
	TGM6	ENST00000381423.1	TSL:1	c.1678+2284C>A		intron	N/A	ENSP00000370831.1

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

African (AFR) AF: 0.118 AC: 4884 AN: 41530

American (AMR) AF: 0.0851 AC: 1302 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0772 AC: 268 AN: 3472

East Asian (EAS) AF: 0.143 AC: 744 AN: 5194

South Asian (SAS) AF: 0.144 AC: 694 AN: 4828

European-Finnish (FIN) AF: 0.0975 AC: 1032 AN: 10590

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0998 AC: 6789 AN: 68010

Other (OTH) AF: 0.103 AC: 217 AN: 2110

Alfa AF: 0.104 Hom.: 1563

Bravo AF: 0.106

Asia WGS AF: 0.141 AC: 493 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.1
DANN	Benign	0.74
PhyloP100		0.30
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: rs10485600; hg19: chr20-2400503;