Variant 11-18701612-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_153347.3(TMEM86A):c.326C>T(p.Ser109Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000014 in 1,429,878 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

TMEM86A
NM_153347.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.64

Variant links:

Genes affected

TMEM86A (HGNC:26890): (transmembrane protein 86A) Predicted to enable alkenylglycerophosphocholine hydrolase activity and alkenylglycerophosphoethanolamine hydrolase activity. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM86A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.15996638).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TMEM86A	NM_153347.3 linkuse as main transcript	c.326C>T	p.Ser109Leu	missense_variant	3/3	ENST00000280734.3	NP_699178.1
TMEM86A	XM_047426448.1 linkuse as main transcript	c.326C>T	p.Ser109Leu	missense_variant	3/4		XP_047282404.1
TMEM86A	XM_047426449.1 linkuse as main transcript	c.326C>T	p.Ser109Leu	missense_variant	3/5		XP_047282405.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
TMEM86A	ENST00000280734.3 linkuse as main transcript	c.326C>T	p.Ser109Leu	missense_variant	3/3	1	NM_153347.3	ENSP00000280734	P1
TMEM86A	ENST00000527002.5 linkuse as main transcript	n.561C>T		non_coding_transcript_exon_variant	3/3	4
TMEM86A	ENST00000529240.1 linkuse as main transcript	n.446C>T		non_coding_transcript_exon_variant	3/3	4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000434

AC:

AN:

230510

Hom.:

AF XY:

0.00000808

AC XY:

AN XY:

123786

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000312

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:

0.00000140

AC:

AN:

1429878

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

707192

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.00000183

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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

Mar 19, 2024

The c.326C>T (p.S109L) alteration is located in exon 3 (coding exon 3) of the TMEM86A gene. This alteration results from a C to T substitution at nucleotide position 326, causing the serine (S) at amino acid position 109 to be replaced by a leucine (L). 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

0.14

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Benign

0.85

DEOGEN2

Benign

0.0076

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.069

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.86

M_CAP

Benign

0.0090

MetaRNN

Benign

0.16

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.91

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.69

PROVEAN

Benign

-0.50

REVEL

Benign

0.090

Sift

Benign

0.66

Sift4G

Benign

0.67

Polyphen

0.0080

Vest4

0.36

MutPred

0.44

Loss of glycosylation at S109 (P = 0.0163);

MVP

0.12

MPC

0.37

ClinPred

0.24

GERP RS

4.1

Varity_R

0.082

gMVP

0.61

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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