NM_199337.3:c.452C>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_199337.3(TMEM179B):​c.452C>T​(p.Pro151Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Consequence

TMEM179B
NM_199337.3 missense

Scores

1
7
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.69
Variant links:
Genes affected
TMEM179B (HGNC:33744): (transmembrane protein 179B) Located in nuclear speck and nucleolus. [provided by Alliance of Genome Resources, Apr 2022]
TMEM223 (HGNC:28464): (transmembrane protein 223) Predicted to be involved in nervous system development. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]
MIR6748 (HGNC:50141): (microRNA 6748) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.26760906).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TMEM179BNM_199337.3 linkc.452C>T p.Pro151Leu missense_variant Exon 4 of 5 ENST00000333449.9 NP_955369.1 Q7Z7N9

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TMEM179BENST00000333449.9 linkc.452C>T p.Pro151Leu missense_variant Exon 4 of 5 1 NM_199337.3 ENSP00000333697.3 Q7Z7N9

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
31
Bravo
AF:
0.00000378

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Mar 23, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.452C>T (p.P151L) alteration is located in exon 4 (coding exon 4) of the TMEM179B gene. This alteration results from a C to T substitution at nucleotide position 452, causing the proline (P) at amino acid position 151 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
Benign
0.14
BayesDel_addAF
Uncertain
0.054
T
BayesDel_noAF
Benign
-0.16
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.21
T
Eigen
Uncertain
0.40
Eigen_PC
Uncertain
0.37
FATHMM_MKL
Benign
0.38
N
LIST_S2
Benign
0.85
T
M_CAP
Benign
0.010
T
MetaRNN
Benign
0.27
T
MetaSVM
Benign
-0.48
T
MutationAssessor
Uncertain
2.5
M
PrimateAI
Benign
0.35
T
PROVEAN
Uncertain
-2.5
N
REVEL
Benign
0.18
Sift
Uncertain
0.0090
D
Sift4G
Pathogenic
0.0
D
Polyphen
0.96
D
Vest4
0.28
MutPred
0.40
Loss of glycosylation at P151 (P = 0.0309);
MVP
0.33
MPC
0.095
ClinPred
0.96
D
GERP RS
5.9
Varity_R
0.11
gMVP
0.31

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: rs2084334668; hg19: chr11-62557105; API