3-44901823-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003241.4(TGM4):​c.863G>A​(p.Ser288Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000477 in 1,614,108 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00032 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000020 ( 0 hom. )

Consequence

TGM4
NM_003241.4 missense

Scores

6
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.101
Variant links:
Genes affected
TGM4 (HGNC:11780): (transglutaminase 4) Predicted to enable protein-glutamine gamma-glutamyltransferase activity. Predicted to be involved in peptide cross-linking. Predicted to act upstream of or within mating plug formation. Located in Golgi apparatus and collagen-containing extracellular matrix. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.12242252).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TGM4NM_003241.4 linkuse as main transcriptc.863G>A p.Ser288Asn missense_variant 8/14 ENST00000296125.9 NP_003232.2
TGM4XM_011534042.3 linkuse as main transcriptc.998G>A p.Ser333Asn missense_variant 9/15 XP_011532344.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TGM4ENST00000296125.9 linkuse as main transcriptc.863G>A p.Ser288Asn missense_variant 8/141 NM_003241.4 ENSP00000296125 P2
TGM4ENST00000705784.1 linkuse as main transcriptc.998G>A p.Ser333Asn missense_variant 9/15 ENSP00000516167 A2

Frequencies

GnomAD3 genomes
AF:
0.000309
AC:
47
AN:
152154
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000821
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000851
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000716
AC:
18
AN:
251348
Hom.:
0
AF XY:
0.0000662
AC XY:
9
AN XY:
135878
show subpopulations
Gnomad AFR exome
AF:
0.000985
Gnomad AMR exome
AF:
0.0000578
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000198
AC:
29
AN:
1461836
Hom.:
0
Cov.:
64
AF XY:
0.0000151
AC XY:
11
AN XY:
727220
show subpopulations
Gnomad4 AFR exome
AF:
0.000627
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000360
Gnomad4 OTH exome
AF:
0.0000497
GnomAD4 genome
AF:
0.000315
AC:
48
AN:
152272
Hom.:
0
Cov.:
33
AF XY:
0.000390
AC XY:
29
AN XY:
74452
show subpopulations
Gnomad4 AFR
AF:
0.000842
Gnomad4 AMR
AF:
0.000850
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000772
Hom.:
0
Bravo
AF:
0.000223
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000741
AC:
9

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsApr 14, 2022The c.863G>A (p.S288N) alteration is located in exon 8 (coding exon 8) of the TGM4 gene. This alteration results from a G to A substitution at nucleotide position 863, causing the serine (S) at amino acid position 288 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.42
BayesDel_addAF
Benign
-0.42
T
BayesDel_noAF
Benign
-0.42
CADD
Benign
16
DANN
Benign
0.96
DEOGEN2
Uncertain
0.60
D
Eigen
Benign
-0.51
Eigen_PC
Benign
-0.82
FATHMM_MKL
Benign
0.11
N
M_CAP
Benign
0.039
D
MetaRNN
Benign
0.12
T
MetaSVM
Uncertain
-0.054
T
MutationAssessor
Uncertain
2.4
M
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.43
T
PROVEAN
Benign
-2.3
N
REVEL
Benign
0.28
Sift
Uncertain
0.022
D
Sift4G
Uncertain
0.052
T
Polyphen
1.0
D
Vest4
0.11
MVP
0.78
MPC
0.40
ClinPred
0.073
T
GERP RS
-1.9
Varity_R
0.45
gMVP
0.21

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs182325252; hg19: chr3-44943315; API