Variant 12-108591875-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_181724.3(TMEM119):c.509G>A(p.Arg170Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000116 in 1,609,928 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00012 ( 0 hom. )

Consequence

TMEM119
NM_181724.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.763

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 Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.010635167).

BP6

Variant 12-108591875-C-T is Benign according to our data. Variant chr12-108591875-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2567944.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM119	NM_181724.3 linkuse as main transcript	c.509G>A	p.Arg170Gln	missense_variant	2/2	ENST00000392806.4	NP_859075.2
TMEM119	XM_011538271.3 linkuse as main transcript	c.509G>A	p.Arg170Gln	missense_variant	3/3		XP_011536573.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM119	ENST00000392806.4 linkuse as main transcript	c.509G>A	p.Arg170Gln	missense_variant	2/2	1	NM_181724.3	ENSP00000376553	P1

Frequencies

GnomAD3 genomes

AF:

0.0000789

AC:

AN:

152052

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000327

AC:

AN:

245014

Hom.:

AF XY:

0.0000225

AC XY:

AN XY:

133336

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000548

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000633

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000120

AC:

175

AN:

1457758

Hom.:

Cov.:

AF XY:

0.000130

AC XY:

AN XY:

724924

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000449

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000148

Gnomad4 OTH exome

AF:

0.000116

GnomAD4 genome

AF:

0.0000789

AC:

AN:

152170

Hom.:

Cov.:

AF XY:

0.0000806

AC XY:

AN XY:

74396

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000840

Hom.:

Bravo

AF:

0.0000416

ExAC

AF:

0.0000412

AC:

EpiCase

AF:

0.000218

EpiControl

AF:

0.000178

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 20, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.68

CADD

Benign

DANN

Benign

0.87

DEOGEN2

Benign

0.0031

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.84

FATHMM_MKL

Benign

0.20

LIST_S2

Benign

0.62

M_CAP

Benign

0.0044

MetaRNN

Benign

0.011

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.6

MutationTaster

Benign

1.0

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.040

REVEL

Benign

0.036

Sift

Benign

0.86

Sift4G

Benign

0.46

Polyphen

0.043

Vest4

0.067

MutPred

0.15

Loss of MoRF binding (P = 0.0764);

MVP

0.23

MPC

0.15

ClinPred

0.043

GERP RS

0.11

Varity_R

0.029

gMVP

0.038

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