chr3-149333244-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_138786.4(TM4SF18):​c.139G>T​(p.Val47Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,842 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. V47M) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

TM4SF18
NM_138786.4 missense

Scores

2
7
10

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.70
Variant links:
Genes affected
TM4SF18 (HGNC:25181): (transmembrane 4 L six family member 18) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]
TM4SF18-AS1 (HGNC:56678): (TM4SF18 antisense RNA 1)

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TM4SF18NM_138786.4 linkc.139G>T p.Val47Leu missense_variant Exon 2 of 6 ENST00000296059.7 NP_620141.1 Q96CE8
TM4SF18NM_001184723.2 linkc.139G>T p.Val47Leu missense_variant Exon 1 of 5 NP_001171652.1 Q96CE8
TM4SF18-AS1NR_186251.1 linkn.405-260C>A intron_variant Intron 1 of 1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TM4SF18ENST00000296059.7 linkc.139G>T p.Val47Leu missense_variant Exon 2 of 6 1 NM_138786.4 ENSP00000296059.2 Q96CE8

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1460842
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
726700
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.:
31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.57
BayesDel_addAF
Uncertain
0.094
D
BayesDel_noAF
Benign
-0.10
CADD
Benign
22
DANN
Uncertain
1.0
DEOGEN2
Benign
0.33
T;T;T
Eigen
Benign
0.093
Eigen_PC
Benign
0.19
FATHMM_MKL
Uncertain
0.81
D
LIST_S2
Benign
0.84
.;T;T
M_CAP
Benign
0.0074
T
MetaRNN
Uncertain
0.47
T;T;T
MetaSVM
Benign
-0.72
T
MutationAssessor
Pathogenic
3.3
M;M;.
PrimateAI
Benign
0.48
T
PROVEAN
Uncertain
-2.5
N;N;D
REVEL
Benign
0.25
Sift
Uncertain
0.019
D;D;D
Sift4G
Uncertain
0.012
D;D;.
Polyphen
0.0030
B;B;.
Vest4
0.41
MutPred
0.57
Gain of helix (P = 0.062);Gain of helix (P = 0.062);Gain of helix (P = 0.062);
MVP
0.12
MPC
0.15
ClinPred
0.98
D
GERP RS
4.6
Varity_R
0.23
gMVP
0.66

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: chr3-149051031; API