17-30325028-C-T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_206832.3(TMIGD1):​c.428G>A​(p.Cys143Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,818 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. C143F) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

TMIGD1
NM_206832.3 missense

Scores

12
4
3

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.10
Variant links:
Genes affected
TMIGD1 (HGNC:32431): (transmembrane and immunoglobulin domain containing 1) Involved in several processes, including negative regulation of apoptotic process; regulation of cell migration; and regulation of membrane permeability. Located in cytoplasm and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.993

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TMIGD1NM_206832.3 linkc.428G>A p.Cys143Tyr missense_variant Exon 4 of 7 ENST00000328886.5 NP_996663.1 Q6UXZ0-1
TMIGD1NM_001319942.2 linkc.428G>A p.Cys143Tyr missense_variant Exon 4 of 6 NP_001306871.1 Q6UXZ0-2
TMIGD1XM_011524787.2 linkc.428G>A p.Cys143Tyr missense_variant Exon 4 of 7 XP_011523089.1 Q6UXZ0-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TMIGD1ENST00000328886.5 linkc.428G>A p.Cys143Tyr missense_variant Exon 4 of 7 1 NM_206832.3 ENSP00000332404.4 Q6UXZ0-1
TMIGD1ENST00000538566.6 linkc.428G>A p.Cys143Tyr missense_variant Exon 4 of 6 2 ENSP00000446118.2 Q6UXZ0-2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461818
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
727210
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:
0.00000180
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
0.99
BayesDel_addAF
Pathogenic
0.41
D
BayesDel_noAF
Pathogenic
0.35
CADD
Uncertain
25
DANN
Uncertain
0.99
DEOGEN2
Benign
0.35
.;T
Eigen
Pathogenic
0.89
Eigen_PC
Pathogenic
0.75
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Benign
0.78
T;T
M_CAP
Pathogenic
0.53
D
MetaRNN
Pathogenic
0.99
D;D
MetaSVM
Pathogenic
0.99
D
MutationAssessor
Pathogenic
4.3
H;H
PrimateAI
Uncertain
0.72
T
PROVEAN
Pathogenic
-11
D;D
REVEL
Pathogenic
0.73
Sift
Uncertain
0.0030
D;D
Sift4G
Pathogenic
0.0
D;D
Polyphen
1.0
D;D
Vest4
0.98
MutPred
0.90
Loss of ubiquitination at K146 (P = 0.0768);Loss of ubiquitination at K146 (P = 0.0768);
MVP
0.95
MPC
0.26
ClinPred
1.0
D
GERP RS
5.8
Varity_R
0.90
gMVP
0.95

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: chr17-28652046; API