chr4-153586227-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_001131007.2(TMEM131L):c.1330C>T(p.Pro444Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000446 in 1,570,102 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000042 ( 0 hom. )
Consequence
TMEM131L
NM_001131007.2 missense
NM_001131007.2 missense
Scores
3
10
6
Clinical Significance
Conservation
PhyloP100: 5.34
Genes affected
TMEM131L (HGNC:29146): (transmembrane 131 like) Involved in negative regulation of canonical Wnt signaling pathway and negative regulation of immature T cell proliferation in thymus. 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 Uncertain_significance. Variant got 3 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.803
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TMEM131L | NM_001131007.2 | c.1330C>T | p.Pro444Ser | missense_variant | 14/35 | ENST00000409959.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TMEM131L | ENST00000409959.8 | c.1330C>T | p.Pro444Ser | missense_variant | 14/35 | 5 | NM_001131007.2 | A2 | |
TMEM131L | ENST00000240487.5 | c.913C>T | p.Pro305Ser | missense_variant | 10/29 | 1 | |||
TMEM131L | ENST00000409663.7 | c.1327C>T | p.Pro443Ser | missense_variant | 14/35 | 5 | P4 | ||
TMEM131L | ENST00000509565.1 | n.405C>T | non_coding_transcript_exon_variant | 4/4 | 4 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 151986Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.00000423 AC: 6AN: 1418116Hom.: 0 Cov.: 30 AF XY: 0.00000142 AC XY: 1AN XY: 703514
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GnomAD4 genome ? AF: 0.00000658 AC: 1AN: 151986Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74226
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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 submitter | clinical testing | Ambry Genetics | Mar 08, 2024 | The c.1330C>T (p.P444S) alteration is located in exon 14 (coding exon 14) of the KIAA0922 gene. This alteration results from a C to T substitution at nucleotide position 1330, causing the proline (P) at amino acid position 444 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
Cadd
Uncertain
Dann
Pathogenic
DEOGEN2
Benign
T;.;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D;D
MetaSVM
Uncertain
T
MutationAssessor
Uncertain
M;.;.
MutationTaster
Benign
D;D;N
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;D
REVEL
Uncertain
Sift
Benign
T;T;T
Sift4G
Benign
T;T;T
Polyphen
P;P;.
Vest4
MutPred
Loss of glycosylation at P448 (P = 0.08);.;.;
MVP
MPC
0.49
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at