1-203014922-C-T

Variant summary

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

The ENST00000367242.4(TMEM183A):​c.401C>T​(p.Pro134Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

TMEM183A
ENST00000367242.4 missense

Scores

12
5
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.91
Variant links:
Genes affected
TMEM183A (HGNC:20173): (transmembrane protein 183A) Predicted to be involved in regulation of protein stability. Predicted to be integral component of membrane. Predicted to be part of SCF ubiquitin ligase complex. [provided by Alliance of Genome Resources, Apr 2022]

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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, 0.845

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TMEM183ANM_138391.6 linkuse as main transcriptc.401C>T p.Pro134Leu missense_variant 4/8 ENST00000367242.4 NP_612400.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TMEM183AENST00000367242.4 linkuse as main transcriptc.401C>T p.Pro134Leu missense_variant 4/81 NM_138391.6 ENSP00000356211 P1Q8IXX5-1
TMEM183AENST00000463015.1 linkuse as main transcriptn.105C>T non_coding_transcript_exon_variant 2/22
TMEM183AENST00000468449.5 linkuse as main transcriptn.292C>T non_coding_transcript_exon_variant 3/53
TMEM183AENST00000543891.5 linkuse as main transcriptn.663C>T non_coding_transcript_exon_variant 3/43

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

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 07, 2023The c.401C>T (p.P134L) alteration is located in exon 4 (coding exon 4) of the TMEM183A gene. This alteration results from a C to T substitution at nucleotide position 401, causing the proline (P) at amino acid position 134 to be replaced by a leucine (L). 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
Pathogenic
0.87
BayesDel_addAF
Pathogenic
0.44
D
BayesDel_noAF
Pathogenic
0.40
CADD
Pathogenic
29
DANN
Uncertain
1.0
DEOGEN2
Benign
0.41
T
Eigen
Pathogenic
0.91
Eigen_PC
Pathogenic
0.89
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Pathogenic
0.98
D
M_CAP
Uncertain
0.11
D
MetaRNN
Pathogenic
0.85
D
MetaSVM
Uncertain
0.64
D
MutationAssessor
Uncertain
2.7
M
MutationTaster
Benign
1.0
D
PrimateAI
Uncertain
0.75
T
PROVEAN
Pathogenic
-6.6
D
REVEL
Pathogenic
0.89
Sift
Pathogenic
0.0
D
Sift4G
Pathogenic
0.0
D
Polyphen
1.0
D
Vest4
0.84
MutPred
0.57
Loss of loop (P = 0.0031);
MVP
0.76
MPC
1.6
ClinPred
1.0
D
GERP RS
5.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.67
gMVP
0.78

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: chr1-202984050; API