rs10898590

Positions:

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

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM135	NM_022918.4	c.142-3710G>A		intron_variant		ENST00000305494.6	NP_075069.3
TMEM135	NM_001168724.2	c.142-3710G>A		intron_variant			NP_001162195.1
TMEM135	NR_033149.2	n.254-3710G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM135	ENST00000305494.6	c.142-3710G>A		intron_variant		1	NM_022918.4	ENSP00000306344	P1

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

Gnomad4 AFR AF: 0.0853

Gnomad4 AMR AF: 0.0535

Gnomad4 ASJ AF: 0.0568

Gnomad4 EAS AF: 0.174

Gnomad4 SAS AF: 0.108

Gnomad4 FIN AF: 0.107

Gnomad4 NFE AF: 0.0835

Gnomad4 OTH AF: 0.0605

Alfa AF: 0.0772 Hom.: 486

Bravo AF: 0.0803

Asia WGS AF: 0.136 AC: 474 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	3.7
DANN	Benign	0.57

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

Publications

LitVar

Other links and lift over

dbSNP: rs10898590; hg19: chr11-86775026;