Variant 19-55227369-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 ENST00000327042.5(TMEM86B):c.493G>A(p.Gly165Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000906 in 1,599,964 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000092 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000090 ( 0 hom. )

Consequence

TMEM86B
ENST00000327042.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.77

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 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=0.059913725).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM86B	NM_173804.5 linkuse as main transcript	c.493G>A	p.Gly165Ser	missense_variant	3/3	ENST00000327042.5	NP_776165.3	Q8N661
TMEM86B	NM_001372013.1 linkuse as main transcript	c.490G>A	p.Gly164Ser	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.493G>A	p.Gly165Ser	missense_variant	3/3	1	NM_173804.5	ENSP00000321038.3	Q8N661
TMEM86B	ENST00000585416.1 linkuse as main transcript	n.1416G>A		non_coding_transcript_exon_variant	1/1	6
ENSG00000276570	ENST00000586923.1 linkuse as main transcript	n.2911G>A		non_coding_transcript_exon_variant	1/1	6
TMEM86B	ENST00000589190.1 linkuse as main transcript	n.778G>A		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

AF:

0.0000920

AC:

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.000753

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000109

AC:

AN:

219742

Hom.:

AF XY:

0.000117

AC XY:

AN XY:

119290

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000108

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000356

Gnomad FIN exome

AF:

0.000381

Gnomad NFE exome

AF:

0.000154

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000905

AC:

131

AN:

1447694

Hom.:

Cov.:

AF XY:

0.0000960

AC XY:

AN XY:

718840

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000469

Gnomad4 ASJ exome

AF:

0.0000389

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000118

Gnomad4 FIN exome

AF:

0.000407

Gnomad4 NFE exome

AF:

0.0000905

Gnomad4 OTH exome

AF:

0.000101

GnomAD4 genome

AF:

0.0000919

AC:

AN:

152270

Hom.:

Cov.:

AF XY:

0.000134

AC XY:

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000753

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000122

Hom.:

Bravo

AF:

0.0000529

ExAC

AF:

0.000149

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

Jun 24, 2022

The c.493G>A (p.G165S) 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 493, causing the glycine (G) at amino acid position 165 to be replaced by a serine (S). 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

0.13

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.023

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.26

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.72

M_CAP

Benign

0.017

MetaRNN

Benign

0.060

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.78

MutationTaster

Benign

0.57

PrimateAI

Benign

0.43

PROVEAN

Benign

-1.9

REVEL

Benign

0.070

Sift

Benign

0.15

Sift4G

Benign

0.27

Polyphen

0.77

Vest4

0.11

MVP

0.17

MPC

0.018

ClinPred

0.11

GERP RS

3.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.13

gMVP

0.52

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