rs17222895

Variant names:

• chr20-2381132-G-T
• rs17222895
• NM_198994.3:c.7+157G>T

Your query was ambiguous. Multiple possible variants found:

• chr20-2381132-G-T
• chr20-2381132-G-A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_198994.3(TGM6):​c.7+157G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0197 in 152,246 control chromosomes in the GnomAD database, including 42 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency: Genomes: 𝑓 0.020 (42 hom., cov: 32)
• Consequence: TGM6 NM_198994.3 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.818
• 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: PanelApp Australia, Orphanet, Ambry Genetics, Illumina, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 20-2381132-G-T is Benign according to our data. Variant chr20-2381132-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1326244.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.0197 (2994/152246) while in subpopulation AMR AF = 0.0327 (501/15298). AF 95% confidence interval is 0.0304. There are 42 homozygotes in GnomAd4. There are 1473 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 2994 AD gene.

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.7+157G>T		intron	N/A	NP_945345.2	O95932-1
	TGM6	NM_001254734.2		c.7+157G>T		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.7+157G>T		intron	N/A	ENSP00000202625.2	O95932-1
	TGM6	ENST00000381423.1	TSL:1	c.7+157G>T		intron	N/A	ENSP00000370831.1	O95932-2

Frequencies

GnomAD3 genomes AF: 0.0197 AC: 2994 AN: 152128 Hom.: 42 Cov.: 32

Gnomad AFR AF: 0.0202

Gnomad AMI AF: 0.0186

Gnomad AMR AF: 0.0327

Gnomad ASJ AF: 0.0323

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00228

Gnomad FIN AF: 0.0208

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0180

Gnomad OTH AF: 0.0234

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

GnomAD4 genome AF: 0.0197 AC: 2994 AN: 152246 Hom.: 42 Cov.: 32 AF XY: 0.0198 AC XY: 1473 AN XY: 74432

African (AFR) AF: 0.0202 AC: 839 AN: 41534

American (AMR) AF: 0.0327 AC: 501 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0323 AC: 112 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00207 AC: 10 AN: 4830

European-Finnish (FIN) AF: 0.0208 AC: 221 AN: 10608

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0180 AC: 1221 AN: 68018

Other (OTH) AF: 0.0232 AC: 49 AN: 2116

Alfa AF: 0.00763 Hom.: 2

Bravo AF: 0.0219

Asia WGS AF: 0.00346 AC: 12 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.8
DANN	Benign	0.79
PhyloP100		-0.82
PromoterAI		-0.045	Neutral
Mutation Taster		=100/0	polymorphism

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: rs17222895; hg19: chr20-2361778;