Variant 19-55320979-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_001282011.2(TMEM150B):c.58G>A(p.Val20Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000417 in 1,613,884 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V20F) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00043 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00042 ( 0 hom. )

Consequence

TMEM150B
NM_001282011.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.13

Variant links:

Genes affected

TMEM150B (HGNC:34415): (transmembrane protein 150B) This gene encodes a protein that belongs to the DRAM (damage-regulated autophagy modulator) family of membrane-spanning proteins. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

TMEM150B 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=0.009761602).

BP6

Variant 19-55320979-C-T is Benign according to our data. Variant chr19-55320979-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2304774.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM150B	NM_001282011.2 linkuse as main transcript	c.58G>A	p.Val20Ile	missense_variant	3/8	ENST00000326652.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM150B	ENST00000326652.9 linkuse as main transcript	c.58G>A	p.Val20Ile	missense_variant	3/8	1	NM_001282011.2	P1

Frequencies

GnomAD3 genomes

AF:

0.000434

AC:

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000579

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000853

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000530

AC:

132

AN:

248994

Hom.:

AF XY:

0.000503

AC XY:

AN XY:

135090

show subpopulations

Gnomad AFR exome

AF:

0.000194

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00100

Gnomad SAS exome

AF:

0.000196

Gnomad FIN exome

AF:

0.0000928

Gnomad NFE exome

AF:

0.000859

Gnomad OTH exome

AF:

0.000331

GnomAD4 exome

AF:

0.000415

AC:

607

AN:

1461612

Hom.:

Cov.:

AF XY:

0.000426

AC XY:

310

AN XY:

727122

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000428

Gnomad4 SAS exome

AF:

0.000151

Gnomad4 FIN exome

AF:

0.0000562

Gnomad4 NFE exome

AF:

0.000491

Gnomad4 OTH exome

AF:

0.000298

GnomAD4 genome

AF:

0.000433

AC:

AN:

152272

Hom.:

Cov.:

AF XY:

0.000416

AC XY:

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000580

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000853

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.000701

Hom.:

Bravo

AF:

0.000348

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.000237

AC:

ESP6500EA

AF:

0.000941

AC:

ExAC

AF:

0.000528

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000491

EpiControl

AF:

0.000296

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

Oct 06, 2021

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

0.074

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.73

Cadd

Benign

0.72

Dann

Benign

0.22

DEOGEN2

Benign

0.17

T;.

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0047

LIST_S2

Benign

0.59

T;T

M_CAP

Benign

0.0028

MetaRNN

Benign

0.0098

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-0.33

N;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.33

PROVEAN

Benign

0.44

N;.

REVEL

Benign

0.023

Sift

Benign

1.0

T;.

Sift4G

Benign

1.0

T;.

Polyphen

0.0020

B;.

Vest4

0.051

MVP

0.014

MPC

0.079

ClinPred

0.00089

GERP RS

-3.8

Varity_R

0.030

gMVP

0.29

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