chr11-18701809-A-G

Position:

• chr11-18701809-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_153347.3(TMEM86A):​c.523A>G​(p.Thr175Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TMEM86A NM_153347.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.93

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM86A	NM_153347.3	c.523A>G	p.Thr175Ala	missense_variant	3/3	ENST00000280734.3	NP_699178.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM86A	ENST00000280734.3	c.523A>G	p.Thr175Ala	missense_variant	3/3	1	NM_153347.3	ENSP00000280734.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 30, 2024

The c.523A>G (p.T175A) alteration is located in exon 3 (coding exon 3) of the TMEM86A gene. This alteration results from a A to G substitution at nucleotide position 523, causing the threonine (T) at amino acid position 175 to be replaced by an alanine (A). 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	0.16
BayesDel_addAF	Uncertain	0.045	T
BayesDel_noAF	Benign	-0.17
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.018	T
Eigen	Uncertain	0.63
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.011	T
MetaRNN	Uncertain	0.73	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.24
Sift	Uncertain	0.0040	D
Sift4G	Benign	0.073	T
Polyphen		0.99	D
Vest4		0.69
MutPred		0.63		Loss of loop (P = 0.0203);
MVP		0.12
MPC		1.2
ClinPred		0.92	D
GERP RS		5.4
Varity_R		0.32
gMVP		0.70

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-18723356;