rs470744

Positions:

• chr11-87250803-A-G
• chr11-87250803-A-T

Variant summary

Our verdict is Benign. Variant got -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

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 (NFE) allele frequency at 95% confidence interval = 0.702 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM135	NM_022918.4	c.509+14119A>G		intron_variant		ENST00000305494.6	NP_075069.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM135	ENST00000305494.6	c.509+14119A>G		intron_variant		1	NM_022918.4	ENSP00000306344	P1
TMEM135	ENST00000340353.11	c.443+14119A>G		intron_variant		1		ENSP00000345513
TMEM135	ENST00000525018.5	c.397-26350A>G		intron_variant		5		ENSP00000433927
TMEM135	ENST00000532959.5	c.122+14119A>G		intron_variant		2		ENSP00000436179

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

Gnomad4 AFR AF: 0.665

Gnomad4 AMR AF: 0.574

Gnomad4 ASJ AF: 0.746

Gnomad4 EAS AF: 0.311

Gnomad4 SAS AF: 0.657

Gnomad4 FIN AF: 0.591

Gnomad4 NFE AF: 0.707

Gnomad4 OTH AF: 0.635

Alfa AF: 0.693 Hom.: 4579

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

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: rs470744; hg19: chr11-86961845;