rs148854519

Variant names:

• chr20-2395391-C-G
• rs148854519
• NM_198994.3:c.379C>G

Your query was ambiguous. Multiple possible variants found:

• chr20-2395391-C-G
• chr20-2395391-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_198994.3(TGM6):​c.379C>G​(p.Arg127Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R127Q) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TGM6 NM_198994.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0680
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20624366).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TGM6	NM_198994.3	c.379C>G	p.Arg127Gly	missense_variant	Exon 3 of 13	ENST00000202625.7	NP_945345.2
TGM6	NM_001254734.2	c.379C>G	p.Arg127Gly	missense_variant	Exon 3 of 12		NP_001241663.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TGM6	ENST00000202625.7	c.379C>G	p.Arg127Gly	missense_variant	Exon 3 of 13	1	NM_198994.3	ENSP00000202625.2
TGM6	ENST00000381423.1	c.379C>G	p.Arg127Gly	missense_variant	Exon 3 of 12	1		ENSP00000370831.1
TGM6	ENST00000477505.1	n.174+766C>G		intron_variant	Intron 1 of 3	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.013	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	14
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0065	T;.
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.58
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.64	T;T
M_CAP	Benign	0.055	D
MetaRNN	Benign	0.21	T;T
MetaSVM	Benign	-0.79	T
MutationAssessor	Benign	0.55	N;N
PhyloP100		-0.068
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-2.2	N;N
REVEL	Uncertain	0.30
Sift	Benign	0.23	T;T
Sift4G	Benign	0.39	T;T
Polyphen		0.0010	B;B
Vest4		0.53
MutPred		0.45		Loss of MoRF binding (P = 0.0202);Loss of MoRF binding (P = 0.0202);
MVP		0.49
MPC		0.11
ClinPred		0.088	T
GERP RS		2.3
Varity_R		0.097
gMVP		0.46
Mutation Taster		=43/57	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs148854519; hg19: chr20-2376037;