rs34972666

Variant names:

• chr20-2404326-A-G
• rs34972666
• NM_198994.3:c.1336+503A>G

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+503A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.166 in 152,206 control chromosomes in the GnomAD database, including 2,553 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 0.17 (2553 hom., cov: 33)
• Consequence: TGM6 NM_198994.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.432
• Publications: 9 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: PanelApp Australia, Orphanet, Ambry Genetics, Illumina, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.289 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TGM6	NM_198994.3	MANE Select	c.1336+503A>G		intron	N/A	NP_945345.2	O95932-1
	TGM6	NM_001254734.2		c.1336+503A>G		intron	N/A	NP_001241663.1	O95932-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TGM6	ENST00000202625.7	TSL:1 MANE Select	c.1336+503A>G		intron	N/A	ENSP00000202625.2	O95932-1
	TGM6	ENST00000381423.1	TSL:1	c.1336+503A>G		intron	N/A	ENSP00000370831.1	O95932-2

Frequencies

GnomAD3 genomes AF: 0.166 AC: 25250 AN: 152088 Hom.: 2548 Cov.: 33

Gnomad AFR AF: 0.293

Gnomad AMI AF: 0.0406

Gnomad AMR AF: 0.113

Gnomad ASJ AF: 0.0905

Gnomad EAS AF: 0.190

Gnomad SAS AF: 0.140

Gnomad FIN AF: 0.116

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.149

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

GnomAD4 genome AF: 0.166 AC: 25284 AN: 152206 Hom.: 2553 Cov.: 33 AF XY: 0.164 AC XY: 12242 AN XY: 74444

African (AFR) AF: 0.293 AC: 12164 AN: 41508

American (AMR) AF: 0.113 AC: 1723 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0905 AC: 314 AN: 3468

East Asian (EAS) AF: 0.190 AC: 983 AN: 5170

South Asian (SAS) AF: 0.140 AC: 673 AN: 4822

European-Finnish (FIN) AF: 0.116 AC: 1230 AN: 10606

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.115 AC: 7821 AN: 68012

Other (OTH) AF: 0.147 AC: 310 AN: 2114

Alfa AF: 0.140 Hom.: 2824

Bravo AF: 0.175

Asia WGS AF: 0.169 AC: 589 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.4
DANN	Benign	0.63
PhyloP100		-0.43
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: rs34972666; hg19: chr20-2384972;