rs11853991

Positions:

• chr15-43265351-A-G
• chr15-43265351-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000220420.10(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 ENST00000220420.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.307

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 Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TGM5	NM_201631.4	c.10+1489T>C		intron_variant		ENST00000220420.10	NP_963925.2
TGM5	NM_004245.4	c.10+1489T>C		intron_variant			NP_004236.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TGM5	ENST00000220420.10	c.10+1489T>C		intron_variant		1	NM_201631.4	ENSP00000220420	P1
TGM5	ENST00000349114.8	c.10+1489T>C		intron_variant		1		ENSP00000220419

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

Gnomad4 AFR AF: 0.266

Gnomad4 AMR AF: 0.310

Gnomad4 ASJ AF: 0.405

Gnomad4 EAS AF: 0.311

Gnomad4 SAS AF: 0.390

Gnomad4 FIN AF: 0.202

Gnomad4 NFE AF: 0.311

Gnomad4 OTH AF: 0.317

Alfa AF: 0.315 Hom.: 10245

Bravo AF: 0.304

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.2
DANN	Benign	0.70

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

LitVar

Other links and lift over

dbSNP: rs11853991; hg19: chr15-43557549;