rs2236512

Positions:

• chr1-54053434-G-A
• chr1-54053434-G-C
• chr1-54053434-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001305049.1(TMEM59):​c.-283C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0566 in 530,300 control chromosomes in the GnomAD database, including 2,718 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 0.11 (2000 hom., cov: 32)
  • Exomes 𝑓: 0.037 (718 hom.)
• Consequence: TMEM59 NM_001305049.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.82

Genes affected

TMEM59 (HGNC:1239): (transmembrane protein 59) This gene encodes a protein shown to regulate autophagy in response to bacterial infection. This protein may also regulate the retention of amyloid precursor protein (APP) in the Golgi apparatus through its control of APP glycosylation. Overexpression of this protein has been found to promote apoptosis in a glioma cell line. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.303 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM59	NM_001305049.1	c.-283C>T		5_prime_UTR_variant	1/8		NP_001291978.1
TMEM59	NM_001305051.1	c.-283C>T		5_prime_UTR_variant	1/8		NP_001291980.1
TMEM59	NM_001305052.1	c.-177C>T		5_prime_UTR_variant	1/7		NP_001291981.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM59	ENST00000371341.5	c.-283C>T		5_prime_UTR_variant	1/8	2		ENSP00000360392
TMEM59	ENST00000440019.5	c.-177C>T		5_prime_UTR_variant	1/6	2		ENSP00000399761
TMEM59	ENST00000420738.5			upstream_gene_variant		3		ENSP00000413792
TMEM59	ENST00000452421.5			upstream_gene_variant		5		ENSP00000397772

Frequencies

GnomAD3 genomes AF: 0.106 AC: 16112 AN: 152116 Hom.: 1996 Cov.: 32

Gnomad AFR AF: 0.308

Gnomad AMI AF: 0.0318

Gnomad AMR AF: 0.0433

Gnomad ASJ AF: 0.0285

Gnomad EAS AF: 0.0403

Gnomad SAS AF: 0.0474

Gnomad FIN AF: 0.0300

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0240

Gnomad OTH AF: 0.0832

GnomAD4 exome AF: 0.0368 AC: 13894 AN: 378066 Hom.: 718 Cov.: 4 AF XY: 0.0358 AC XY: 7055 AN XY: 196852

Gnomad4 AFR exome AF: 0.304

Gnomad4 AMR exome AF: 0.0310

Gnomad4 ASJ exome AF: 0.0270

Gnomad4 EAS exome AF: 0.0336

Gnomad4 SAS exome AF: 0.0450

Gnomad4 FIN exome AF: 0.0261

Gnomad4 NFE exome AF: 0.0237

Gnomad4 OTH exome AF: 0.0512

GnomAD4 genome AF: 0.106 AC: 16147 AN: 152234 Hom.: 2000 Cov.: 32 AF XY: 0.105 AC XY: 7815 AN XY: 74438

Gnomad4 AFR AF: 0.308

Gnomad4 AMR AF: 0.0431

Gnomad4 ASJ AF: 0.0285

Gnomad4 EAS AF: 0.0399

Gnomad4 SAS AF: 0.0477

Gnomad4 FIN AF: 0.0300

Gnomad4 NFE AF: 0.0240

Gnomad4 OTH AF: 0.0823

Alfa AF: 0.00593 Hom.: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.5
DANN	Benign	0.87

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: rs2236512; hg19: chr1-54519107;