Variant 19-55227203-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_173804.5(TMEM86B):c.659G>C(p.Ser220Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000349 in 1,531,000 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00022 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00036 ( 0 hom. )

Consequence

TMEM86B
NM_173804.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.709

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:

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=0.014856279).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM86B	NM_173804.5 linkuse as main transcript	c.659G>C	p.Ser220Thr	missense_variant	3/3	ENST00000327042.5	NP_776165.3
TMEM86B	NM_001372013.1 linkuse as main transcript	c.656G>C	p.Ser219Thr	missense_variant	2/2		NP_001358942.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
TMEM86B	ENST00000327042.5 linkuse as main transcript	c.659G>C	p.Ser220Thr	missense_variant	3/3	1	NM_173804.5	ENSP00000321038	P1
TMEM86B	ENST00000585416.1 linkuse as main transcript	n.1582G>C		non_coding_transcript_exon_variant	1/1
TMEM86B	ENST00000589190.1 linkuse as main transcript	n.944G>C		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

AF:

0.000217

AC:

AN:

152124

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:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000412

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000294

AC:

AN:

177086

Hom.:

AF XY:

0.000299

AC XY:

AN XY:

93792

show subpopulations

Gnomad AFR exome

AF:

0.0000795

Gnomad AMR exome

AF:

0.000271

Gnomad ASJ exome

AF:

0.00111

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000628

Gnomad NFE exome

AF:

0.000471

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000363

AC:

501

AN:

1378876

Hom.:

Cov.:

AF XY:

0.000351

AC XY:

237

AN XY:

675036

show subpopulations

Gnomad4 AFR exome

AF:

0.0000629

Gnomad4 AMR exome

AF:

0.000304

Gnomad4 ASJ exome

AF:

0.000958

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000201

Gnomad4 NFE exome

AF:

0.000403

Gnomad4 OTH exome

AF:

0.000495

GnomAD4 genome

AF:

0.000217

AC:

AN:

152124

Hom.:

Cov.:

AF XY:

0.000135

AC XY:

AN XY:

74312

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000412

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000332

Hom.:

Bravo

AF:

0.000219

ESP6500AA

AF:

0.000228

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000290

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

May 13, 2024

The c.659G>C (p.S220T) alteration is located in exon 3 (coding exon 3) of the TMEM86B gene. This alteration results from a G to C substitution at nucleotide position 659, causing the serine (S) at amino acid position 220 to be replaced by a threonine (T). 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

0.081

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.74

CADD

Benign

1.7

DANN

Benign

0.88

DEOGEN2

Benign

0.027

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.24

LIST_S2

Benign

0.25

M_CAP

Benign

0.0033

MetaRNN

Benign

0.015

MetaSVM

Benign

-0.99

MutationAssessor

Benign

2.0

MutationTaster

Benign

1.0

PrimateAI

Benign

0.30

PROVEAN

Benign

-1.5

REVEL

Benign

0.037

Sift

Uncertain

0.027

Sift4G

Uncertain

0.039

Polyphen

0.0040

Vest4

0.073

MVP

0.088

MPC

0.0074

ClinPred

0.014

GERP RS

-2.6

Varity_R

0.085

gMVP

0.22

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