chr15-43265351-A-G

Variant names:

• chr15-43265351-A-G
• rs11853991
• NM_201631.4:c.10+1489T>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.10+1489T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.296 in 152,156 control chromosomes in the GnomAD database, including 7,018 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 0.30 (7018 hom., cov: 33)
• Consequence: TGM5 NM_201631.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.307
• Publications: 18 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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.375 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_201631.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TGM5	NM_201631.4	MANE Select	c.10+1489T>C		intron	N/A	NP_963925.2
	TGM5	NM_004245.4		c.10+1489T>C		intron	N/A	NP_004236.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TGM5	ENST00000220420.10	TSL:1 MANE Select	c.10+1489T>C		intron	N/A	ENSP00000220420.5
	TGM5	ENST00000349114.8	TSL:1	c.10+1489T>C		intron	N/A	ENSP00000220419.8

Frequencies

GnomAD3 genomes AF: 0.296 AC: 44984 AN: 152038 Hom.: 7007 Cov.: 33

Gnomad AFR AF: 0.265

Gnomad AMI AF: 0.286

Gnomad AMR AF: 0.311

Gnomad ASJ AF: 0.405

Gnomad EAS AF: 0.312

Gnomad SAS AF: 0.388

Gnomad FIN AF: 0.202

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.312

Gnomad OTH AF: 0.311

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

GnomAD4 genome AF: 0.296 AC: 45025 AN: 152156 Hom.: 7018 Cov.: 33 AF XY: 0.294 AC XY: 21893 AN XY: 74382

African (AFR) AF: 0.266 AC: 11021 AN: 41506

American (AMR) AF: 0.310 AC: 4740 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.405 AC: 1405 AN: 3466

East Asian (EAS) AF: 0.311 AC: 1612 AN: 5180

South Asian (SAS) AF: 0.390 AC: 1879 AN: 4820

European-Finnish (FIN) AF: 0.202 AC: 2135 AN: 10586

Middle Eastern (MID) AF: 0.422 AC: 124 AN: 294

European-Non Finnish (NFE) AF: 0.311 AC: 21181 AN: 67998

Other (OTH) AF: 0.317 AC: 668 AN: 2110

Alfa AF: 0.315 Hom.: 12981

Bravo AF: 0.304

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.2
DANN	Benign	0.70
PhyloP100		-0.31
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: rs11853991; hg19: chr15-43557549;