Variant 19-55227371-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The ENST00000327042.5(TMEM86B):c.491G>A(p.Arg164His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000324 in 1,599,988 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00022 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00034 ( 0 hom. )

Consequence

TMEM86B
ENST00000327042.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.888

Variant links:

Genes affected

TMEM86B (HGNC:28448): (transmembrane protein 86B) Enables alkenylglycerophosphocholine hydrolase activity; alkenylglycerophosphoethanolamine hydrolase activity; and identical protein binding activity. Involved in ether lipid metabolic process. Located in cytoplasm and membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM86B links:

TMEM86B (HGNC:):

TMEM86B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2858446).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM86B	NM_173804.5 linkuse as main transcript	c.491G>A	p.Arg164His	missense_variant	3/3	ENST00000327042.5	NP_776165.3	Q8N661
TMEM86B	NM_001372013.1 linkuse as main transcript	c.488G>A	p.Arg163His	missense_variant	2/2		NP_001358942.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TMEM86B	ENST00000327042.5 linkuse as main transcript	c.491G>A	p.Arg164His	missense_variant	3/3	1	NM_173804.5	ENSP00000321038.3	Q8N661
TMEM86B	ENST00000585416.1 linkuse as main transcript	n.1414G>A		non_coding_transcript_exon_variant	1/1	6
ENSG00000276570	ENST00000586923.1 linkuse as main transcript	n.2909G>A		non_coding_transcript_exon_variant	1/1	6
TMEM86B	ENST00000589190.1 linkuse as main transcript	n.776G>A		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

AF:

0.000223

AC:

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.000470

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000264

AC:

AN:

219328

Hom.:

AF XY:

0.000235

AC XY:

AN XY:

118956

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000635

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:

0.000557

Gnomad OTH exome

AF:

0.000370

GnomAD4 exome

AF:

0.000335

AC:

485

AN:

1447676

Hom.:

Cov.:

AF XY:

0.000320

AC XY:

230

AN XY:

718872

show subpopulations

Gnomad4 AFR exome

AF:

0.0000600

Gnomad4 AMR exome

AF:

0.0000469

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000237

Gnomad4 FIN exome

AF:

0.0000194

Gnomad4 NFE exome

AF:

0.000418

Gnomad4 OTH exome

AF:

0.000268

GnomAD4 genome

AF:

0.000223

AC:

AN:

152312

Hom.:

Cov.:

AF XY:

0.000242

AC XY:

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.0000241

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:

0.000470

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000503

Hom.:

Bravo

AF:

0.000212

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000216

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

Jan 04, 2024

The c.491G>A (p.R164H) alteration is located in exon 3 (coding exon 3) of the TMEM86B gene. This alteration results from a G to A substitution at nucleotide position 491, causing the arginine (R) at amino acid position 164 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

0.26

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.31

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.11

Eigen

Pathogenic

0.69

Eigen_PC

Uncertain

0.55

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.85

M_CAP

Benign

0.046

MetaRNN

Benign

0.29

MetaSVM

Benign

-0.44

MutationAssessor

Pathogenic

3.6

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.62

PROVEAN

Pathogenic

-4.8

REVEL

Uncertain

0.37

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.0090

Polyphen

1.0

Vest4

0.38

MVP

0.45

MPC

0.037

ClinPred

0.47

GERP RS

4.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.86

gMVP

0.46

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