rs16957511

Variant names:

• chr15-43247919-C-A
• rs16957511
• NM_201631.4:c.862+4840G>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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

Y_RNA (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TGM5	NM_201631.4	MANE Select	c.862+4840G>T		intron	N/A	NP_963925.2
	TGM5	NM_004245.4		c.616+4840G>T		intron	N/A	NP_004236.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TGM5	ENST00000220420.10	TSL:1 MANE Select	c.862+4840G>T		intron	N/A	ENSP00000220420.5
	TGM5	ENST00000349114.8	TSL:1	c.616+4840G>T		intron	N/A	ENSP00000220419.8
	TGM5	ENST00000635871.1	TSL:4	n.331+4840G>T		intron	N/A

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

African (AFR) AF: 0.180 AC: 7465 AN: 41502

American (AMR) AF: 0.124 AC: 1895 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0755 AC: 262 AN: 3472

East Asian (EAS) AF: 0.209 AC: 1086 AN: 5188

South Asian (SAS) AF: 0.115 AC: 557 AN: 4830

European-Finnish (FIN) AF: 0.0947 AC: 1001 AN: 10570

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0931 AC: 6334 AN: 68010

Other (OTH) AF: 0.119 AC: 251 AN: 2112

Alfa AF: 0.102 Hom.: 460

Bravo AF: 0.132

Asia WGS AF: 0.170 AC: 591 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.8
DANN	Benign	0.58
PhyloP100		-0.079
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: rs16957511; hg19: chr15-43540117;