11-87250803-A-G

Variant names:

• chr11-87250803-A-G
• rs470744
• NM_022918.4:c.509+14119A>G

Variant summary

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

The NM_022918.4(TMEM135):​c.509+14119A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.659 in 152,048 control chromosomes in the GnomAD database, including 33,617 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 0.66 (33617 hom., cov: 33)
• Consequence: TMEM135 NM_022918.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.885
• Publications: 1 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 (NFE) allele frequency at 95% confidence interval = 0.702 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM135	NM_022918.4	c.509+14119A>G		intron_variant	Intron 6 of 14	ENST00000305494.6	NP_075069.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM135	ENST00000305494.6	c.509+14119A>G		intron_variant	Intron 6 of 14	1	NM_022918.4	ENSP00000306344.5
TMEM135	ENST00000340353.11	c.443+14119A>G		intron_variant	Intron 5 of 13	1		ENSP00000345513.6
TMEM135	ENST00000532959.5	c.122+14119A>G		intron_variant	Intron 3 of 11	2		ENSP00000436179.1
TMEM135	ENST00000525018.5	c.397-26350A>G		intron_variant	Intron 4 of 4	5		ENSP00000433927.1

Frequencies

GnomAD3 genomes AF: 0.659 AC: 100156 AN: 151932 Hom.: 33594 Cov.: 33

Gnomad AFR AF: 0.665

Gnomad AMI AF: 0.708

Gnomad AMR AF: 0.575

Gnomad ASJ AF: 0.746

Gnomad EAS AF: 0.310

Gnomad SAS AF: 0.655

Gnomad FIN AF: 0.591

Gnomad MID AF: 0.706

Gnomad NFE AF: 0.707

Gnomad OTH AF: 0.640

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

GnomAD4 genome AF: 0.659 AC: 100226 AN: 152048 Hom.: 33617 Cov.: 33 AF XY: 0.649 AC XY: 48225 AN XY: 74300

African (AFR) AF: 0.665 AC: 27602 AN: 41514

American (AMR) AF: 0.574 AC: 8775 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.746 AC: 2590 AN: 3472

East Asian (EAS) AF: 0.311 AC: 1602 AN: 5156

South Asian (SAS) AF: 0.657 AC: 3164 AN: 4818

European-Finnish (FIN) AF: 0.591 AC: 6239 AN: 10550

Middle Eastern (MID) AF: 0.701 AC: 206 AN: 294

European-Non Finnish (NFE) AF: 0.707 AC: 48065 AN: 67950

Other (OTH) AF: 0.635 AC: 1339 AN: 2108

Alfa AF: 0.692 Hom.: 4749

Bravo AF: 0.654

Asia WGS AF: 0.504 AC: 1754 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	7.8
DANN	Benign	0.76
PhyloP100		0.89
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: rs470744; hg19: chr11-86961845;