chr4-152770188-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_145720.4(TIGD4):​c.817G>C​(p.Asp273His) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,786 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D273N) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

TIGD4
NM_145720.4 missense

Scores

10
4
5

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.54
Variant links:
Genes affected
TIGD4 (HGNC:18335): (tigger transposable element derived 4) The protein encoded by this gene belongs to the tigger subfamily of the pogo superfamily of DNA-mediated transposons in humans. These proteins are related to DNA transposons found in fungi and nematodes, and more distantly to the Tc1 and mariner transposases. They are also very similar to the major mammalian centromere protein B. The exact function of this gene is not known. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.874

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TIGD4NM_145720.4 linkc.817G>C p.Asp273His missense_variant Exon 2 of 2 ENST00000304337.3 NP_663772.1 Q8IY51
TIGD4XM_005262807.5 linkc.817G>C p.Asp273His missense_variant Exon 3 of 3 XP_005262864.1 Q8IY51

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TIGD4ENST00000304337.3 linkc.817G>C p.Asp273His missense_variant Exon 2 of 2 1 NM_145720.4 ENSP00000355162.2 Q8IY51

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461786
Hom.:
0
Cov.:
34
AF XY:
0.00000138
AC XY:
1
AN XY:
727190
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
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:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.81
BayesDel_addAF
Pathogenic
0.29
D
BayesDel_noAF
Pathogenic
0.18
CADD
Pathogenic
26
DANN
Uncertain
0.99
DEOGEN2
Benign
0.075
T
Eigen
Pathogenic
0.88
Eigen_PC
Pathogenic
0.86
FATHMM_MKL
Uncertain
0.97
D
LIST_S2
Benign
0.83
T
M_CAP
Benign
0.014
T
MetaRNN
Pathogenic
0.87
D
MetaSVM
Benign
-0.37
T
MutationAssessor
Pathogenic
3.0
M
PrimateAI
Uncertain
0.53
T
PROVEAN
Pathogenic
-6.0
D
REVEL
Uncertain
0.42
Sift
Pathogenic
0.0
D
Sift4G
Pathogenic
0.0
D
Polyphen
1.0
D
Vest4
0.81
MutPred
0.66
Gain of MoRF binding (P = 0.052);
MVP
0.69
MPC
0.18
ClinPred
0.99
D
GERP RS
6.0
Varity_R
0.92
gMVP
0.65

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-153691340; COSMIC: COSV58550677; API