11-87060165-G-A

Variant names:

• chr11-87060165-G-A
• rs10898589
• NM_022918.4:c.142-7529G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022918.4(TMEM135):​c.142-7529G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0851 in 152,212 control chromosomes in the GnomAD database, including 615 homozygotes. 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: 𝑓 0.085 (615 hom., cov: 33)
• Consequence: TMEM135 NM_022918.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.222
• Publications: 3 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.165 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM135	NM_022918.4	MANE Select	c.142-7529G>A		intron	N/A	NP_075069.3
	TMEM135	NM_001168724.2		c.142-7529G>A		intron	N/A	NP_001162195.1
	TMEM135	NR_033149.2		n.254-7529G>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM135	ENST00000305494.6	TSL:1 MANE Select	c.142-7529G>A		intron	N/A	ENSP00000306344.5
	TMEM135	ENST00000340353.11	TSL:1	c.142-7529G>A		intron	N/A	ENSP00000345513.6
	TMEM135	ENST00000532959.5	TSL:2	c.9+22074G>A		intron	N/A	ENSP00000436179.1

Frequencies

GnomAD3 genomes AF: 0.0850 AC: 12926 AN: 152094 Hom.: 614 Cov.: 33

Gnomad AFR AF: 0.0855

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.0529

Gnomad ASJ AF: 0.0568

Gnomad EAS AF: 0.174

Gnomad SAS AF: 0.108

Gnomad FIN AF: 0.107

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0836

Gnomad OTH AF: 0.0599

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0851 AC: 12953 AN: 152212 Hom.: 615 Cov.: 33 AF XY: 0.0866 AC XY: 6443 AN XY: 74430

African (AFR) AF: 0.0857 AC: 3557 AN: 41526

American (AMR) AF: 0.0530 AC: 810 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0568 AC: 197 AN: 3470

East Asian (EAS) AF: 0.174 AC: 902 AN: 5180

South Asian (SAS) AF: 0.109 AC: 525 AN: 4828

European-Finnish (FIN) AF: 0.107 AC: 1130 AN: 10606

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0836 AC: 5686 AN: 67998

Other (OTH) AF: 0.0607 AC: 128 AN: 2110

Alfa AF: 0.0547 Hom.: 64

Bravo AF: 0.0803

Asia WGS AF: 0.135 AC: 471 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.8
DANN	Benign	0.60
PhyloP100		0.22
Mutation Taster		=100/0	polymorphism (auto)

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: rs10898589; hg19: chr11-86771207;