rs2748516

Variant names:

• chr14-24261256-A-G
• rs2748516
• NM_000359.3:c.508+439T>C

Your query was ambiguous. Multiple possible variants found:

• chr14-24261256-A-G
• chr14-24261256-A-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000359.3(TGM1):​c.508+439T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.924 in 152,226 control chromosomes in the GnomAD database, including 64,969 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.92 (64969 hom., cov: 32)
• Consequence: TGM1 NM_000359.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.264
• Publications: 9 publications found

Genes affected

TGM1 (HGNC:11777): (transglutaminase 1) The protein encoded by this gene is a membrane protein that catalyzes the addition of an alkyl group from an akylamine to a glutamine residue of a protein, forming an alkylglutamine in the protein. This protein alkylation leads to crosslinking of proteins and catenation of polyamines to proteins. This gene contains either one or two copies of a 22 nt repeat unit in its 3' UTR. Mutations in this gene have been associated with autosomal recessive lamellar ichthyosis (LI) and nonbullous congenital ichthyosiform erythroderma (NCIE). [provided by RefSeq, Jul 2008]

TGM1 Gene-Disease associations (from GenCC):

• autosomal recessive congenital ichthyosis 1

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), Myriad Women’s Health, PanelApp Australia, Genomics England PanelApp
• acral self-healing collodion baby

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• bathing suit ichthyosis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• congenital non-bullous ichthyosiform erythroderma

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• lamellar ichthyosis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• self-healing collodion baby

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 14-24261256-A-G is Benign according to our data. Variant chr14-24261256-A-G is described in ClinVar as Benign. ClinVar VariationId is 1263572.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.933 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TGM1	NM_000359.3	c.508+439T>C		intron_variant	Intron 3 of 14	ENST00000206765.11	NP_000350.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TGM1	ENST00000206765.11	c.508+439T>C		intron_variant	Intron 3 of 14	1	NM_000359.3	ENSP00000206765.6
TGM1	ENST00000544573.5	c.-29+871T>C		intron_variant	Intron 2 of 8	2		ENSP00000439446.1

Frequencies

GnomAD3 genomes AF: 0.924 AC: 140509 AN: 152108 Hom.: 64925 Cov.: 32

Gnomad AFR AF: 0.895

Gnomad AMI AF: 0.932

Gnomad AMR AF: 0.909

Gnomad ASJ AF: 0.977

Gnomad EAS AF: 0.907

Gnomad SAS AF: 0.950

Gnomad FIN AF: 0.937

Gnomad MID AF: 0.927

Gnomad NFE AF: 0.939

Gnomad OTH AF: 0.931

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

GnomAD4 genome AF: 0.924 AC: 140613 AN: 152226 Hom.: 64969 Cov.: 32 AF XY: 0.923 AC XY: 68714 AN XY: 74418

African (AFR) AF: 0.895 AC: 37137 AN: 41506

American (AMR) AF: 0.908 AC: 13888 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.977 AC: 3392 AN: 3472

East Asian (EAS) AF: 0.907 AC: 4703 AN: 5184

South Asian (SAS) AF: 0.949 AC: 4573 AN: 4820

European-Finnish (FIN) AF: 0.937 AC: 9945 AN: 10612

Middle Eastern (MID) AF: 0.922 AC: 271 AN: 294

European-Non Finnish (NFE) AF: 0.939 AC: 63882 AN: 68020

Other (OTH) AF: 0.932 AC: 1972 AN: 2116

Alfa AF: 0.938 Hom.: 112258

Bravo AF: 0.921

Asia WGS AF: 0.932 AC: 3244 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	6.3
DANN	Benign	0.65
PhyloP100		0.26
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2748516; hg19: chr14-24730462;