rs597319

chr11-87142955-A-Gchr11-87142955-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.397-14386A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.361 in 149,986 control chromosomes in the GnomAD database, including 10,298 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 0.36 (10298 hom., cov: 28)
• Consequence: TMEM135 NM_022918.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.47

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=-1.04).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.653 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM135	NM_022918.4	c.397-14386A>G		intron_variant		ENST00000305494.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM135	ENST00000305494.6	c.397-14386A>G		intron_variant		1	NM_022918.4	P1

Frequencies

GnomAD3 genomes AF: 0.361 AC: 54084 AN: 149868 Hom.: 10287 Cov.: 28

Gnomad AFR AF: 0.398

Gnomad AMI AF: 0.385

Gnomad AMR AF: 0.458

Gnomad ASJ AF: 0.309

Gnomad EAS AF: 0.672

Gnomad SAS AF: 0.429

Gnomad FIN AF: 0.296

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.299

Gnomad OTH AF: 0.389

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

GnomAD4 genome AF: 0.361 AC: 54137 AN: 149986 Hom.: 10298 Cov.: 28 AF XY: 0.367 AC XY: 26836 AN XY: 73080

Gnomad4 AFR AF: 0.398

Gnomad4 AMR AF: 0.459

Gnomad4 ASJ AF: 0.309

Gnomad4 EAS AF: 0.672

Gnomad4 SAS AF: 0.429

Gnomad4 FIN AF: 0.296

Gnomad4 NFE AF: 0.299

Gnomad4 OTH AF: 0.392

Alfa AF: 0.319 Hom.: 1043

Bravo AF: 0.374

Asia WGS AF: 0.520 AC: 1806 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.84
Dann	Benign	0.34
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs597319; hg19: chr11-86853997;