15-43234871-G-C

Variant names:

• chr15-43234871-G-C
• rs142648722
• NM_201631.4:c.1773C>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_201631.4(TGM5):​c.1773C>G​(p.Asp591Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: TGM5 NM_201631.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.96

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.42132097).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TGM5	NM_201631.4	c.1773C>G	p.Asp591Glu	missense_variant	Exon 11 of 13	ENST00000220420.10	NP_963925.2
TGM5	NM_004245.4	c.1527C>G	p.Asp509Glu	missense_variant	Exon 10 of 12		NP_004236.1
TGM5	XM_011522230.3	c.744C>G	p.Asp248Glu	missense_variant	Exon 5 of 7		XP_011520532.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TGM5	ENST00000220420.10	c.1773C>G	p.Asp591Glu	missense_variant	Exon 11 of 13	1	NM_201631.4	ENSP00000220420.5
TGM5	ENST00000349114.8	c.1527C>G	p.Asp509Glu	missense_variant	Exon 10 of 12	1		ENSP00000220419.8
TGM5	ENST00000396996.3	n.1249C>G		non_coding_transcript_exon_variant	Exon 4 of 6	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.47
BayesDel_addAF	Benign	-0.018	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.077	T;T;T;.;.
Eigen	Benign	0.14
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.44	T;T;T;T;T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.42	T;T;T;T;T
MetaSVM	Benign	-0.59	T
MutationAssessor	Benign	2.0	.;.;M;.;.
PrimateAI	Uncertain	0.52	T
PROVEAN	Uncertain	-2.6	.;.;D;.;D
REVEL	Benign	0.12
Sift	Benign	0.37	.;.;T;.;T
Sift4G	Benign	0.28	T;T;T;T;T
Polyphen		0.17, 0.36	.;.;B;.;B
Vest4		0.62, 0.62
MutPred		0.56		.;.;Loss of stability (P = 0.0394);.;.;
MVP		0.52
MPC		0.60
ClinPred		0.98	D
GERP RS		4.8
Varity_R		0.47
gMVP		0.25

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs142648722; hg19: chr15-43527069;