Variant 19-55227201-G-A 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.661C>T(p.Pro221Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000523 in 1,528,638 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 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000036 ( 0 hom. )

Consequence

TMEM86B
ENST00000327042.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.02

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=0.030072689).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM86B	NM_173804.5 linkuse as main transcript	c.661C>T	p.Pro221Ser	missense_variant	3/3	ENST00000327042.5	NP_776165.3	Q8N661
TMEM86B	NM_001372013.1 linkuse as main transcript	c.658C>T	p.Pro220Ser	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.661C>T	p.Pro221Ser	missense_variant	3/3	1	NM_173804.5	ENSP00000321038.3	Q8N661
TMEM86B	ENST00000585416.1 linkuse as main transcript	n.1584C>T		non_coding_transcript_exon_variant	1/1	6
TMEM86B	ENST00000589190.1 linkuse as main transcript	n.946C>T		non_coding_transcript_exon_variant	2/2	2
ENSG00000276570	ENST00000586923.1 linkuse as main transcript	n.*18C>T		downstream_gene_variant		6

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000575

AC:

AN:

173786

Hom.:

AF XY:

0.0000109

AC XY:

AN XY:

91976

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000393

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000363

AC:

AN:

1376344

Hom.:

Cov.:

AF XY:

0.00000445

AC XY:

AN XY:

673568

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000140

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152294

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

ExAC

AF:

0.00000829

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

Jan 04, 2022

The c.661C>T (p.P221S) alteration is located in exon 3 (coding exon 3) of the TMEM86B gene. This alteration results from a C to T substitution at nucleotide position 661, causing the proline (P) at amino acid position 221 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

0.079

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.60

CADD

Benign

8.0

DANN

Benign

0.93

DEOGEN2

Benign

0.018

Eigen

Benign

-0.81

Eigen_PC

Benign

-0.81

FATHMM_MKL

Benign

0.63

LIST_S2

Benign

0.46

M_CAP

Benign

0.0030

MetaRNN

Benign

0.030

MetaSVM

Benign

-0.95

MutationAssessor

Benign

2.0

MutationTaster

Benign

1.0

PrimateAI

Benign

0.26

PROVEAN

Benign

-2.1

REVEL

Benign

0.060

Sift

Benign

0.083

Sift4G

Uncertain

0.054

Polyphen

0.0080

Vest4

0.066

MutPred

0.26

Gain of phosphorylation at P221 (P = 0.0567);

MVP

0.10

MPC

0.012

ClinPred

0.073

GERP RS

0.86

Varity_R

0.046

gMVP

0.24

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