Variant chr12-108592263-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM1PM2BP4

The ENST00000392806.4(TMEM119):c.121A>G(p.Ser41Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000189 in 1,588,900 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

TMEM119
ENST00000392806.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.69

Variant links:

Genes affected

TMEM119 (HGNC:27884): (transmembrane protein 119) Involved in positive regulation of bone mineralization; positive regulation of osteoblast differentiation; and positive regulation of osteoblast proliferation. Located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM119 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM1

In a glycosylation_site O-linked (GalNAc...) serine (size 0) in uniprot entity TM119_HUMAN

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.39132866).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM119	NM_181724.3 linkuse as main transcript	c.121A>G	p.Ser41Gly	missense_variant	2/2	ENST00000392806.4	NP_859075.2	Q4V9L6
TMEM119	XM_011538271.3 linkuse as main transcript	c.121A>G	p.Ser41Gly	missense_variant	3/3		XP_011536573.1	Q4V9L6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TMEM119	ENST00000392806.4 linkuse as main transcript	c.121A>G	p.Ser41Gly	missense_variant	2/2	1	NM_181724.3	ENSP00000376553.3	Q4V9L6
TMEM119	ENST00000549031.1 linkuse as main transcript	c.121A>G	p.Ser41Gly	missense_variant	3/3	4		ENSP00000448583.1	F8VS22
TMEM119	ENST00000549447.1 linkuse as main transcript	c.121A>G	p.Ser41Gly	missense_variant	3/3	4		ENSP00000447120.1	F8W0W9
TMEM119	ENST00000547567.1 linkuse as main transcript	c.*37A>G		downstream_gene_variant		2		ENSP00000447345.1	F8VZL0

Frequencies

GnomAD3 genomes

AF:

0.00000659

AC:

AN:

151856

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000139

AC:

AN:

1437044

Hom.:

Cov.:

AF XY:

0.00000140

AC XY:

AN XY:

714142

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:

0.00000181

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000659

AC:

AN:

151856

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74178

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 18, 2022

The c.121A>G (p.S41G) alteration is located in exon 2 (coding exon 1) of the TMEM119 gene. This alteration results from a A to G substitution at nucleotide position 121, causing the serine (S) at amino acid position 41 to be replaced by a glycine (G). 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

0.30

BayesDel_addAF

Uncertain

0.042

BayesDel_noAF

Benign

-0.18

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.21

T;.;.

Eigen

Uncertain

0.47

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.64

T;T;T

M_CAP

Benign

0.064

MetaRNN

Benign

0.39

T;T;T

MetaSVM

Benign

-0.40

MutationAssessor

Benign

1.6

L;.;.

MutationTaster

Benign

0.98

PrimateAI

Uncertain

0.54

PROVEAN

Uncertain

-3.4

D;D;D

REVEL

Benign

0.24

Sift

Pathogenic

0.0

D;D;.

Sift4G

Pathogenic

0.0

D;.;D

Polyphen

1.0

D;.;.

Vest4

0.69

MutPred

0.32

Loss of glycosylation at S41 (P = 9e-04);Loss of glycosylation at S41 (P = 9e-04);Loss of glycosylation at S41 (P = 9e-04);

MVP

0.42

MPC

0.56

ClinPred

0.99

GERP RS

4.6

Varity_R

0.73

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over