dbSNP rs767584166: TM4SF18:p.Val47Leu (chr3-149333244-C-A) – ACMG Classification: Uncertain_significance (2 pts)

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

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 links:

TM4SF18-AS1 (HGNC:56678): (TM4SF18 antisense RNA 1)

TM4SF18-AS1 links:

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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
TM4SF18	NM_138786.4 link	c.139G>T	p.Val47Leu	missense_variant	Exon 2 of 6	ENST00000296059.7	NP_620141.1	Q96CE8
TM4SF18	NM_001184723.2 link	c.139G>T	p.Val47Leu	missense_variant	Exon 1 of 5		NP_001171652.1	Q96CE8
TM4SF18-AS1	NR_186251.1 link	n.405-260C>A		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TM4SF18	ENST00000296059.7 link	c.139G>T	p.Val47Leu	missense_variant	Exon 2 of 6	1	NM_138786.4	ENSP00000296059.2		Q96CE8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1460842

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

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.:

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

BayesDel_noAF

Benign

-0.10

CADD

Benign

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

LIST_S2

Benign

0.84

.;T;T

M_CAP

Benign

0.0074

MetaRNN

Uncertain

0.47

T;T;T

MetaSVM

Benign

-0.72

MutationAssessor

Pathogenic

3.3

M;M;.

PrimateAI

Benign

0.48

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

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over