rs597319

Variant names:

• chr11-87142955-A-G
• rs597319
• NM_022918.4:c.397-14386A>G

Your query was ambiguous. Multiple possible variants found:

• chr11-87142955-A-G
• chr11-87142955-A-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 18 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=-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 rank	MANE	Protein	UniProt
TMEM135	NM_022918.4	c.397-14386A>G		intron_variant	Intron 4 of 14	ENST00000305494.6	NP_075069.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM135	ENST00000305494.6	c.397-14386A>G		intron_variant	Intron 4 of 14	1	NM_022918.4	ENSP00000306344.5

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

African (AFR) AF: 0.398 AC: 16221 AN: 40758

American (AMR) AF: 0.459 AC: 6892 AN: 15024

Ashkenazi Jewish (ASJ) AF: 0.309 AC: 1071 AN: 3464

East Asian (EAS) AF: 0.672 AC: 3433 AN: 5110

South Asian (SAS) AF: 0.429 AC: 2047 AN: 4776

European-Finnish (FIN) AF: 0.296 AC: 2947 AN: 9966

Middle Eastern (MID) AF: 0.442 AC: 129 AN: 292

European-Non Finnish (NFE) AF: 0.299 AC: 20229 AN: 67600

Other (OTH) AF: 0.392 AC: 819 AN: 2090

Alfa AF: 0.332 Hom.: 13738

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
PhyloP100		-1.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs597319; hg19: chr11-86853997;