Variant 19-55378025-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_139172.3(TMEM190):c.356C>T(p.Pro119Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000502 in 1,612,770 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 30)

Exomes 𝑓: 0.000039 ( 0 hom. )

Consequence

TMEM190
NM_139172.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.109

Variant links:

Genes affected

TMEM190 (HGNC:29632): (transmembrane protein 190) Predicted to enable protein self-association. Predicted to be involved in hematopoietic progenitor cell differentiation. Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

TMEM190 links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.031696826).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM190	NM_139172.3 linkuse as main transcript	c.356C>T	p.Pro119Leu	missense_variant	5/5	ENST00000291934.4	NP_631911.1
TMEM190	XM_017026331.2 linkuse as main transcript	c.230C>T	p.Pro77Leu	missense_variant	4/4		XP_016881820.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM190	ENST00000291934.4 linkuse as main transcript	c.356C>T	p.Pro119Leu	missense_variant	5/5	1	NM_139172.3	ENSP00000291934	P1
	ENST00000595064.1 linkuse as main transcript	n.101G>A		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes

AF:

0.000151

AC:

AN:

151872

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000484

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:

0.0000945

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000522

AC:

AN:

248850

Hom.:

AF XY:

0.0000444

AC XY:

AN XY:

135016

show subpopulations

Gnomad AFR exome

AF:

0.000375

Gnomad AMR exome

AF:

0.0000869

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000545

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000469

Gnomad NFE exome

AF:

0.00000893

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.0000390

AC:

AN:

1460780

Hom.:

Cov.:

AF XY:

0.0000330

AC XY:

AN XY:

726736

show subpopulations

Gnomad4 AFR exome

AF:

0.000269

Gnomad4 AMR exome

AF:

0.0000895

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000202

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.0000381

Gnomad4 NFE exome

AF:

0.0000198

Gnomad4 OTH exome

AF:

0.000182

GnomAD4 genome

AF:

0.000158

AC:

AN:

151990

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74274

show subpopulations

Gnomad4 AFR

AF:

0.000506

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000945

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000580

Hom.:

Bravo

AF:

0.000110

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000412

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

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

Mar 05, 2024

The c.356C>T (p.P119L) alteration is located in exon 5 (coding exon 5) of the TMEM190 gene. This alteration results from a C to T substitution at nucleotide position 356, causing the proline (P) at amino acid position 119 to be replaced by a leucine (L). 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

0.11

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.58

CADD

Benign

9.0

DANN

Benign

0.81

DEOGEN2

Benign

0.18

Eigen

Benign

-1.9

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.016

LIST_S2

Benign

0.40

M_CAP

Benign

0.0030

MetaRNN

Benign

0.032

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

MutationTaster

Benign

1.0

PrimateAI

Benign

0.27

PROVEAN

Benign

-2.1

REVEL

Benign

0.019

Sift

Benign

0.12

Sift4G

Benign

0.13

Polyphen

0.019

Vest4

0.14

MVP

0.095

MPC

0.45

ClinPred

0.0096

GERP RS

-6.0

Varity_R

0.030

gMVP

0.081

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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