11-18701841-C-T

Variant names:

• chr11-18701841-C-T
• rs146522347
• NM_153347.3:c.555C>T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_153347.3(TMEM86A):​c.555C>T​(p.Phe185Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 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 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.623

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 Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP7: Synonymous conserved (PhyloP=0.623 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM86A	NM_153347.3	c.555C>T	p.Phe185Phe	synonymous_variant	Exon 3 of 3	ENST00000280734.3	NP_699178.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM86A	ENST00000280734.3	c.555C>T	p.Phe185Phe	synonymous_variant	Exon 3 of 3	1	NM_153347.3	ENSP00000280734.2
TMEM86A	ENST00000527002.5	n.*113C>T		downstream_gene_variant		4
TMEM86A	ENST00000529240.1	n.*142C>T		downstream_gene_variant		4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	4.5
DANN	Benign	0.78

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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

Other links and lift over

dbSNP: rs146522347; hg19: chr11-18723388;