Variant 19-55377643-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_139172.3(TMEM190):c.145A>G(p.Ile49Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000118 in 1,613,468 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 30)

Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

TMEM190
NM_139172.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.662

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07173824).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM190	NM_139172.3 linkuse as main transcript	c.145A>G	p.Ile49Val	missense_variant	3/5	ENST00000291934.4	NP_631911.1
TMEM190	XM_017026331.2 linkuse as main transcript	c.95-159A>G		intron_variant			XP_016881820.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM190	ENST00000291934.4 linkuse as main transcript	c.145A>G	p.Ile49Val	missense_variant	3/5	1	NM_139172.3	ENSP00000291934	P1
	ENST00000595064.1 linkuse as main transcript	n.483T>C		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152060

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

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

GnomAD3 exomes

AF:

0.0000120

AC:

AN:

250666

Hom.:

AF XY:

0.00000738

AC XY:

AN XY:

135488

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000753

AC:

AN:

1461290

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

726938

show subpopulations

Gnomad4 AFR exome

AF:

0.000239

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.0000526

AC:

AN:

152178

Hom.:

Cov.:

AF XY:

0.0000806

AC XY:

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.000193

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

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.0000718

ExAC

AF:

0.0000247

AC:

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

Dec 08, 2021

The c.145A>G (p.I49V) alteration is located in exon 3 (coding exon 3) of the TMEM190 gene. This alteration results from a A to G substitution at nucleotide position 145, causing the isoleucine (I) at amino acid position 49 to be replaced by a valine (V). 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

0.083

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.38

CADD

Benign

9.7

DANN

Benign

0.95

DEOGEN2

Benign

0.046

Eigen

Benign

-0.34

Eigen_PC

Benign

-0.37

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.46

M_CAP

Benign

0.019

MetaRNN

Benign

0.072

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.0

MutationTaster

Benign

0.99

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-0.46

REVEL

Benign

0.053

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.74

Vest4

0.24

MutPred

0.22

Loss of catalytic residue at L54 (P = 0.038);

MVP

0.048

MPC

0.40

ClinPred

0.31

GERP RS

2.8

Varity_R

0.12

gMVP

0.33

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