Variant chr22-38221563-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_012264.5(TMEM184B):c.1130G>A(p.Arg377His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00263 in 1,613,994 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0019 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0027 ( 7 hom. )

Consequence

TMEM184B
NM_012264.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.14

Variant links:

Genes affected

TMEM184B (HGNC:1310): (transmembrane protein 184B) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM184B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006246507).

BS2

High Homozygotes in GnomAdExome4 at 7 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM184B	NM_012264.5 linkuse as main transcript	c.1130G>A	p.Arg377His	missense_variant	9/9	ENST00000361906.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM184B	ENST00000361906.8 linkuse as main transcript	c.1130G>A	p.Arg377His	missense_variant	9/9	1	NM_012264.5	P1

Frequencies

GnomAD3 genomes

AF:

0.00192

AC:

292

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000700

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000589

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00359

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00167

AC:

418

AN:

250790

Hom.:

AF XY:

0.00181

AC XY:

246

AN XY:

135630

show subpopulations

Gnomad AFR exome

AF:

0.000863

Gnomad AMR exome

AF:

0.00119

Gnomad ASJ exome

AF:

0.000498

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.000392

Gnomad FIN exome

AF:

0.0000464

Gnomad NFE exome

AF:

0.00289

Gnomad OTH exome

AF:

0.00278

GnomAD4 exome

AF:

0.00271

AC:

3957

AN:

1461666

Hom.:

Cov.:

AF XY:

0.00272

AC XY:

1977

AN XY:

727166

show subpopulations

Gnomad4 AFR exome

AF:

0.000538

Gnomad4 AMR exome

AF:

0.00112

Gnomad4 ASJ exome

AF:

0.000574

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000812

Gnomad4 FIN exome

AF:

0.000375

Gnomad4 NFE exome

AF:

0.00324

Gnomad4 OTH exome

AF:

0.00268

GnomAD4 genome

AF:

0.00192

AC:

292

AN:

152328

Hom.:

Cov.:

AF XY:

0.00185

AC XY:

138

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.000698

Gnomad4 AMR

AF:

0.000588

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.00359

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00272

Hom.:

Bravo

AF:

0.00201

TwinsUK

AF:

0.00297

AC:

ALSPAC

AF:

0.00337

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00430

AC:

ExAC

AF:

0.00150

AC:

182

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00322

EpiControl

AF:

0.00350

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

Sep 01, 2021

The c.1130G>A (p.R377H) alteration is located in exon 9 (coding exon 8) of the TMEM184B gene. This alteration results from a G to A substitution at nucleotide position 1130, causing the arginine (R) at amino acid position 377 to be replaced by a histidine (H). 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

0.082

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.016

T;T

Eigen

Benign

0.090

Eigen_PC

Benign

0.098

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.71

.;T

M_CAP

Benign

0.011

MetaRNN

Benign

0.0062

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.0

L;L

MutationTaster

Benign

1.0

D;D

PrimateAI

Benign

0.45

PROVEAN

Benign

0.060

N;N

REVEL

Benign

0.073

Sift

Benign

0.084

T;T

Sift4G

Benign

0.44

T;T

Polyphen

0.99

D;D

Vest4

0.076

MVP

0.12

MPC

0.67

ClinPred

0.020

GERP RS

4.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.051

gMVP

0.58

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