rs10898590

Variant names:

• chr11-87063984-G-A
• rs10898590
• NM_022918.4:c.142-3710G>A

Your query was ambiguous. Multiple possible variants found:

• chr11-87063984-G-A
• chr11-87063984-G-C

Variant summary

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

The NM_022918.4(TMEM135):​c.142-3710G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.085 in 152,140 control chromosomes in the GnomAD database, including 607 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 (607 hom., cov: 32)
• Consequence: TMEM135 NM_022918.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.321
• Publications: 2 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=-0.91).
• 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM135	NM_022918.4	MANE Select	c.142-3710G>A		intron	N/A	NP_075069.3
	TMEM135	NM_001168724.2		c.142-3710G>A		intron	N/A	NP_001162195.1	Q86UB9-2
	TMEM135	NR_033149.2		n.254-3710G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM135	ENST00000305494.6	TSL:1 MANE Select	c.142-3710G>A		intron	N/A	ENSP00000306344.5	Q86UB9-1
	TMEM135	ENST00000340353.11	TSL:1	c.142-3710G>A		intron	N/A	ENSP00000345513.6	Q86UB9-2
	TMEM135	ENST00000954970.1		c.142-3710G>A		intron	N/A	ENSP00000625029.1

Frequencies

GnomAD3 genomes AF: 0.0849 AC: 12906 AN: 152022 Hom.: 606 Cov.: 32

Gnomad AFR AF: 0.0851

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.0534

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: 0.0835

Gnomad OTH AF: 0.0598

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

GnomAD4 genome AF: 0.0850 AC: 12933 AN: 152140 Hom.: 607 Cov.: 32 AF XY: 0.0864 AC XY: 6428 AN XY: 74358

African (AFR) AF: 0.0853 AC: 3541 AN: 41508

American (AMR) AF: 0.0535 AC: 817 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0568 AC: 197 AN: 3468

East Asian (EAS) AF: 0.174 AC: 904 AN: 5182

South Asian (SAS) AF: 0.108 AC: 522 AN: 4816

European-Finnish (FIN) AF: 0.107 AC: 1128 AN: 10578

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

European-Non Finnish (NFE) AF: 0.0835 AC: 5678 AN: 67992

Other (OTH) AF: 0.0605 AC: 128 AN: 2114

Alfa AF: 0.0775 Hom.: 572

Bravo AF: 0.0803

Asia WGS AF: 0.136 AC: 474 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.7
DANN	Benign	0.57
PhyloP100		0.32
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: rs10898590; hg19: chr11-86775026;