15-43235685-G-C

Variant names:

• chr15-43235685-G-C
• NM_201631.4:c.1498C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_201631.4(TGM5):​c.1498C>G​(p.Arg500Gly) 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 1,461,888 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TGM5 NM_201631.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.09

Genes affected

TGM5 (HGNC:11781): (transglutaminase 5) This gene encodes a member of the transglutaminase family. The encoded protein catalyzes formation of protein cross-links between glutamine and lysine residues, often resulting in stabilization of protein assemblies. This reaction is calcium dependent. Mutations in this gene have been associated with acral peeling skin syndrome. [provided by RefSeq, Oct 2009]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11031386).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TGM5	NM_201631.4	c.1498C>G	p.Arg500Gly	missense_variant	Exon 10 of 13	ENST00000220420.10	NP_963925.2
TGM5	NM_004245.4	c.1252C>G	p.Arg418Gly	missense_variant	Exon 9 of 12		NP_004236.1
TGM5	XM_011522230.3	c.469C>G	p.Arg157Gly	missense_variant	Exon 4 of 7		XP_011520532.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TGM5	ENST00000220420.10	c.1498C>G	p.Arg500Gly	missense_variant	Exon 10 of 13	1	NM_201631.4	ENSP00000220420.5
TGM5	ENST00000349114.8	c.1252C>G	p.Arg418Gly	missense_variant	Exon 9 of 12	1		ENSP00000220419.8
TGM5	ENST00000396996.3	n.974C>G		non_coding_transcript_exon_variant	Exon 3 of 6	2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461888 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727244

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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.048	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	13
DANN	Uncertain	0.99
DEOGEN2	Benign	0.027	T;T;T;.;.
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.77	T;T;T;T;T
M_CAP	Benign	0.033	D
MetaRNN	Benign	0.11	T;T;T;T;T
MetaSVM	Benign	-0.79	T
MutationAssessor	Benign	0.69	.;.;N;.;.
PrimateAI	Benign	0.20	T
PROVEAN	Benign	-1.7	.;.;N;.;N
REVEL	Benign	0.27
Sift	Uncertain	0.016	.;.;D;.;D
Sift4G	Uncertain	0.031	D;T;T;D;T
Polyphen		0.0010, 0.0040	.;.;B;.;B
Vest4		0.063, 0.064
MutPred		0.28		.;.;Loss of stability (P = 0.0565);.;.;
MVP		0.44
MPC		0.19
ClinPred		0.19	T
GERP RS		5.6
Varity_R		0.084
gMVP		0.39

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-43527883;