rs504417

Variant names:

• chr15-43262028-A-G
• rs504417
• NM_201631.4:c.11-1449T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_201631.4(TGM5):​c.11-1449T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.477 in 151,978 control chromosomes in the GnomAD database, including 22,047 homozygotes. 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: 𝑓 0.48 (22047 hom., cov: 32)
• Consequence: TGM5 NM_201631.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.89
• Publications: 16 publications found

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]

TGM5 Gene-Disease associations (from GenCC):

• acral peeling skin syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, PanelApp Australia, Labcorp Genetics (formerly Invitae), Orphanet, G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.858 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TGM5	NM_201631.4	c.11-1449T>C		intron_variant	Intron 1 of 12	ENST00000220420.10	NP_963925.2
TGM5	NM_004245.4	c.11-1449T>C		intron_variant	Intron 1 of 11		NP_004236.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TGM5	ENST00000220420.10	c.11-1449T>C		intron_variant	Intron 1 of 12	1	NM_201631.4	ENSP00000220420.5
TGM5	ENST00000349114.8	c.11-1449T>C		intron_variant	Intron 1 of 11	1		ENSP00000220419.8

Frequencies

GnomAD3 genomes AF: 0.476 AC: 72321 AN: 151860 Hom.: 21988 Cov.: 32

Gnomad AFR AF: 0.866

Gnomad AMI AF: 0.286

Gnomad AMR AF: 0.381

Gnomad ASJ AF: 0.417

Gnomad EAS AF: 0.398

Gnomad SAS AF: 0.424

Gnomad FIN AF: 0.206

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.319

Gnomad OTH AF: 0.442

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

GnomAD4 genome AF: 0.477 AC: 72436 AN: 151978 Hom.: 22047 Cov.: 32 AF XY: 0.468 AC XY: 34740 AN XY: 74284

African (AFR) AF: 0.866 AC: 35922 AN: 41486

American (AMR) AF: 0.380 AC: 5799 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.417 AC: 1449 AN: 3472

East Asian (EAS) AF: 0.397 AC: 2052 AN: 5164

South Asian (SAS) AF: 0.425 AC: 2042 AN: 4808

European-Finnish (FIN) AF: 0.206 AC: 2175 AN: 10556

Middle Eastern (MID) AF: 0.497 AC: 146 AN: 294

European-Non Finnish (NFE) AF: 0.319 AC: 21651 AN: 67924

Other (OTH) AF: 0.446 AC: 940 AN: 2108

Alfa AF: 0.371 Hom.: 6229

Bravo AF: 0.508

Asia WGS AF: 0.441 AC: 1537 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.12
DANN	Benign	0.55
PhyloP100		-1.9
Mutation Taster		=100/0	polymorphism (auto)

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: rs504417; hg19: chr15-43554226;