20-2410234-C-T

Variant names:

• chr20-2410234-C-T
• rs4053458
• NM_198994.3:c.1336+6411C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_198994.3(TGM6):​c.1336+6411C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 151,978 control chromosomes in the GnomAD database, including 1,938 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 0.15 (1938 hom., cov: 31)
• Consequence: TGM6 NM_198994.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.498
• Publications: 1 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.24 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TGM6	NM_198994.3	c.1336+6411C>T		intron_variant	Intron 9 of 12	ENST00000202625.7	NP_945345.2
TGM6	NM_001254734.2	c.1336+6411C>T		intron_variant	Intron 9 of 11		NP_001241663.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TGM6	ENST00000202625.7	c.1336+6411C>T		intron_variant	Intron 9 of 12	1	NM_198994.3	ENSP00000202625.2
TGM6	ENST00000381423.1	c.1336+6411C>T		intron_variant	Intron 9 of 11	1		ENSP00000370831.1

Frequencies

GnomAD3 genomes AF: 0.153 AC: 23258 AN: 151860 Hom.: 1941 Cov.: 31

Gnomad AFR AF: 0.103

Gnomad AMI AF: 0.0769

Gnomad AMR AF: 0.189

Gnomad ASJ AF: 0.156

Gnomad EAS AF: 0.251

Gnomad SAS AF: 0.165

Gnomad FIN AF: 0.175

Gnomad MID AF: 0.207

Gnomad NFE AF: 0.165

Gnomad OTH AF: 0.161

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

GnomAD4 genome AF: 0.153 AC: 23253 AN: 151978 Hom.: 1938 Cov.: 31 AF XY: 0.153 AC XY: 11390 AN XY: 74260

African (AFR) AF: 0.102 AC: 4249 AN: 41464

American (AMR) AF: 0.188 AC: 2879 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.156 AC: 543 AN: 3470

East Asian (EAS) AF: 0.251 AC: 1289 AN: 5134

South Asian (SAS) AF: 0.163 AC: 784 AN: 4810

European-Finnish (FIN) AF: 0.175 AC: 1849 AN: 10558

Middle Eastern (MID) AF: 0.202 AC: 59 AN: 292

European-Non Finnish (NFE) AF: 0.165 AC: 11185 AN: 67954

Other (OTH) AF: 0.164 AC: 346 AN: 2108

Alfa AF: 0.154 Hom.: 303

Bravo AF: 0.154

Asia WGS AF: 0.217 AC: 755 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	14
DANN	Benign	0.50
PhyloP100		0.50
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: rs4053458; hg19: chr20-2390880;