20-2400410-C-G

Variant names:

• chr20-2400410-C-G
• NM_198994.3:c.955C>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_198994.3(TGM6):​c.955C>G​(p.Arg319Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,870 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R319Q) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TGM6 NM_198994.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.503

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TGM6	NM_198994.3	c.955C>G	p.Arg319Gly	missense_variant	Exon 7 of 13	ENST00000202625.7	NP_945345.2
TGM6	NM_001254734.2	c.955C>G	p.Arg319Gly	missense_variant	Exon 7 of 12		NP_001241663.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TGM6	ENST00000202625.7	c.955C>G	p.Arg319Gly	missense_variant	Exon 7 of 13	1	NM_198994.3	ENSP00000202625.2
TGM6	ENST00000381423.1	c.955C>G	p.Arg319Gly	missense_variant	Exon 7 of 12	1		ENSP00000370831.1
TGM6	ENST00000477505.1	n.586C>G		non_coding_transcript_exon_variant	Exon 4 of 4	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461870 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727234

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.37
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.030
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.32	T;.
Eigen	Benign	0.11
Eigen_PC	Benign	-0.020
FATHMM_MKL	Benign	0.36	N
LIST_S2	Benign	0.78	T;T
M_CAP	Uncertain	0.090	D
MetaRNN	Uncertain	0.55	D;D
MetaSVM	Uncertain	0.34	D
MutationAssessor	Benign	1.6	L;L
PrimateAI	Benign	0.31	T
PROVEAN	Uncertain	-4.4	D;D
REVEL	Uncertain	0.53
Sift	Uncertain	0.0090	D;D
Sift4G	Uncertain	0.014	D;D
Polyphen		0.99	D;D
Vest4		0.36
MutPred		0.54		Loss of stability (P = 0.0789);Loss of stability (P = 0.0789);
MVP		0.80
MPC		0.41
ClinPred		0.98	D
GERP RS		1.1
Varity_R		0.38
gMVP		0.47

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-2381056;