rs34972666

Positions:

• chr20-2404326-A-G

Variant summary

Our verdict is Benign. Variant got -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

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.289 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TGM6	NM_198994.3	c.1336+503A>G		intron_variant		ENST00000202625.7	NP_945345.2
TGM6	NM_001254734.2	c.1336+503A>G		intron_variant			NP_001241663.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TGM6	ENST00000202625.7	c.1336+503A>G		intron_variant		1	NM_198994.3	ENSP00000202625	P1
TGM6	ENST00000381423.1	c.1336+503A>G		intron_variant		1		ENSP00000370831

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

Gnomad4 AFR AF: 0.293

Gnomad4 AMR AF: 0.113

Gnomad4 ASJ AF: 0.0905

Gnomad4 EAS AF: 0.190

Gnomad4 SAS AF: 0.140

Gnomad4 FIN AF: 0.116

Gnomad4 NFE AF: 0.115

Gnomad4 OTH AF: 0.147

Alfa AF: 0.133 Hom.: 298

Bravo AF: 0.175

Asia WGS AF: 0.169 AC: 589 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.4
DANN	Benign	0.63

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: rs34972666; hg19: chr20-2384972;