rs16957511

chr15-43247919-C-A

Variant summary

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

The NM_201631.4(TGM5):c.862+4840G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 152,184 control chromosomes in the GnomAD database, including 1,327 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 0.12 (1327 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: TGM5 NM_201631.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0790

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.199 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TGM5	NM_201631.4	c.862+4840G>T		intron_variant		ENST00000220420.10
TGM5	NM_004245.4	c.616+4840G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TGM5	ENST00000220420.10	c.862+4840G>T		intron_variant		1	NM_201631.4	P1
TGM5	ENST00000349114.8	c.616+4840G>T		intron_variant		1
TGM5	ENST00000635871.1	n.331+4840G>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.124 AC: 18921 AN: 152066 Hom.: 1320 Cov.: 32

Gnomad AFR AF: 0.180

Gnomad AMI AF: 0.0954

Gnomad AMR AF: 0.124

Gnomad ASJ AF: 0.0755

Gnomad EAS AF: 0.210

Gnomad SAS AF: 0.115

Gnomad FIN AF: 0.0947

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0932

Gnomad OTH AF: 0.112

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

GnomAD4 genome AF: 0.125 AC: 18962 AN: 152184 Hom.: 1327 Cov.: 32 AF XY: 0.126 AC XY: 9363 AN XY: 74394

Gnomad4 AFR AF: 0.180

Gnomad4 AMR AF: 0.124

Gnomad4 ASJ AF: 0.0755

Gnomad4 EAS AF: 0.209

Gnomad4 SAS AF: 0.115

Gnomad4 FIN AF: 0.0947

Gnomad4 NFE AF: 0.0931

Gnomad4 OTH AF: 0.119

Alfa AF: 0.102 Hom.: 423

Bravo AF: 0.132

Asia WGS AF: 0.170 AC: 591 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	2.8
Dann	Benign	0.58

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: rs16957511; hg19: chr15-43540117;