11-87309595-C-A

Variant names:

• chr11-87309595-C-A
• rs750838526
• NM_022918.4:c.859C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4 BP7

The NM_022918.4(TMEM135):​c.859C>A​(p.Arg287Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,588 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: TMEM135 NM_022918.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.66
• Publications: 0 publications found

Genes affected

TMEM135 (HGNC:26167): (transmembrane protein 135) Predicted to be involved in peroxisome organization. Predicted to act upstream of or within response to cold and response to food. Predicted to be located in mitochondrion and peroxisome. [provided by Alliance of Genome Resources, Apr 2022]

TMEM135 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder

  Inheritance: AR Classification: LIMITED Submitted by: G2P

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.16).
• BP7: Synonymous conserved (PhyloP=1.66 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022918.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM135	NM_022918.4	MANE Select	c.859C>A	p.Arg287Arg	synonymous	Exon 10 of 15	NP_075069.3
	TMEM135	NM_001168724.2		c.793C>A	p.Arg265Arg	synonymous	Exon 9 of 14	NP_001162195.1	Q86UB9-2
	TMEM135	NR_033149.2		n.937C>A		non_coding_transcript_exon	Exon 9 of 14

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM135	ENST00000305494.6	TSL:1 MANE Select	c.859C>A	p.Arg287Arg	synonymous	Exon 10 of 15	ENSP00000306344.5	Q86UB9-1
	TMEM135	ENST00000340353.11	TSL:1	c.793C>A	p.Arg265Arg	synonymous	Exon 9 of 14	ENSP00000345513.6	Q86UB9-2
	TMEM135	ENST00000954970.1		c.904C>A	p.Arg302Arg	synonymous	Exon 11 of 16	ENSP00000625029.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461588 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727114

African (AFR) AF: 0.00 AC: 0 AN: 33470

American (AMR) AF: 0.00 AC: 0 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26122

East Asian (EAS) AF: 0.00 AC: 0 AN: 39674

South Asian (SAS) AF: 0.00 AC: 0 AN: 86244

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53402

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111804

Other (OTH) AF: 0.00 AC: 0 AN: 60386

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.16
CADD	Benign	5.7
DANN	Benign	0.67
PhyloP100		1.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

Other links and lift over

dbSNP: rs750838526; hg19: chr11-87020637;