rs201913296

Variant names:

• chr12-108591875-C-A
• rs201913296
• NM_181724.3:c.509G>T

Your query was ambiguous. Multiple possible variants found:

• chr12-108591875-C-A
• chr12-108591875-C-G
• chr12-108591875-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_181724.3(TMEM119):​c.509G>T​(p.Arg170Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,758 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. 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. R170W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: TMEM119 NM_181724.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.763
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.058130383).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181724.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM119	NM_181724.3	MANE Select	c.509G>T	p.Arg170Leu	missense	Exon 2 of 2	NP_859075.2	Q4V9L6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM119	ENST00000392806.4	TSL:1 MANE Select	c.509G>T	p.Arg170Leu	missense	Exon 2 of 2	ENSP00000376553.3	Q4V9L6
	TMEM119	ENST00000861158.1		c.509G>T	p.Arg170Leu	missense	Exon 3 of 3	ENSP00000531217.1
	TMEM119	ENST00000861159.1		c.509G>T	p.Arg170Leu	missense	Exon 3 of 3	ENSP00000531218.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1457758 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 724924

African (AFR) AF: 0.00 AC: 0 AN: 33378

American (AMR) AF: 0.00 AC: 0 AN: 44526

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25944

East Asian (EAS) AF: 0.00 AC: 0 AN: 39660

South Asian (SAS) AF: 0.00 AC: 0 AN: 86094

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51822

Middle Eastern (MID) AF: 0.000175 AC: 1 AN: 5724

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110424

Other (OTH) AF: 0.00 AC: 0 AN: 60186

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.059	T
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.64
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.58	T
M_CAP	Benign	0.0094	T
MetaRNN	Benign	0.058	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.76
PrimateAI	Benign	0.30	T
PROVEAN	Uncertain	-3.5	D
REVEL	Benign	0.035
Sift	Benign	0.083	T
Sift4G	Benign	0.19	T
Polyphen		0.011	B
Vest4		0.19
MutPred		0.22		Loss of solvent accessibility (P = 0.0544)
MVP		0.27
MPC		0.19
ClinPred		0.15	T
GERP RS		0.11
Varity_R		0.16
gMVP		0.065
Mutation Taster		=82/18	polymorphism

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

Other links and lift over

dbSNP: rs201913296; hg19: chr12-108985651;