chr14-24260894-A-C

Variant names:

• chr14-24260894-A-C
• rs7151201
• NM_000359.3:c.509-196T>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000359.3(TGM1):​c.509-196T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 152,234 control chromosomes in the GnomAD database, including 1,926 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.15 (1926 hom., cov: 33)
• Consequence: TGM1 NM_000359.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.93
• Publications: 12 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant 14-24260894-A-C is Benign according to our data. Variant chr14-24260894-A-C is described in ClinVar as Benign. ClinVar VariationId is 1230006.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.19 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TGM1	NM_000359.3	c.509-196T>G		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.509-196T>G		intron_variant	Intron 3 of 14	1	NM_000359.3	ENSP00000206765.6
TGM1	ENST00000544573.5	c.-29+1233T>G		intron_variant	Intron 2 of 8	2		ENSP00000439446.1

Frequencies

GnomAD3 genomes AF: 0.154 AC: 23468 AN: 152116 Hom.: 1927 Cov.: 33

Gnomad AFR AF: 0.0966

Gnomad AMI AF: 0.190

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.213

Gnomad EAS AF: 0.0864

Gnomad SAS AF: 0.124

Gnomad FIN AF: 0.131

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.193

Gnomad OTH AF: 0.169

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

GnomAD4 genome AF: 0.154 AC: 23478 AN: 152234 Hom.: 1926 Cov.: 33 AF XY: 0.150 AC XY: 11152 AN XY: 74430

African (AFR) AF: 0.0966 AC: 4013 AN: 41550

American (AMR) AF: 0.171 AC: 2616 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.213 AC: 739 AN: 3472

East Asian (EAS) AF: 0.0862 AC: 446 AN: 5176

South Asian (SAS) AF: 0.124 AC: 599 AN: 4824

European-Finnish (FIN) AF: 0.131 AC: 1394 AN: 10612

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.193 AC: 13110 AN: 67996

Other (OTH) AF: 0.170 AC: 358 AN: 2112

Alfa AF: 0.185 Hom.: 4550

Bravo AF: 0.157

Asia WGS AF: 0.105 AC: 364 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 19, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	20
DANN	Benign	0.45
PhyloP100		2.9
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: rs7151201; hg19: chr14-24730100;