1-54053434-G-C

Variant names:

• chr1-54053434-G-C
• rs2236512
• NM_001305049.1:c.-283C>G

Variant summary

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

The NM_001305049.1(TMEM59):​c.-283C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.052 in 530,254 control chromosomes in the GnomAD database, including 2,927 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 0.055 (738 hom., cov: 32)
  • Exomes 𝑓: 0.051 (2189 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.317 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM59	NM_001305049.1	c.-283C>G		5_prime_UTR_variant	Exon 1 of 8		NP_001291978.1
TMEM59	NM_001305051.1	c.-283C>G		5_prime_UTR_variant	Exon 1 of 8		NP_001291980.1
TMEM59	NM_001305052.1	c.-177C>G		5_prime_UTR_variant	Exon 1 of 7		NP_001291981.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM59	ENST00000371341.5	c.-283C>G		5_prime_UTR_variant	Exon 1 of 8	2		ENSP00000360392.1
TMEM59	ENST00000440019.5	c.-177C>G		5_prime_UTR_variant	Exon 1 of 6	2		ENSP00000399761.1
TMEM59	ENST00000452421.5	c.-246C>G		upstream_gene_variant		5		ENSP00000397772.1
TMEM59	ENST00000420738.5	c.-316C>G		upstream_gene_variant		3		ENSP00000413792.1

Frequencies

GnomAD3 genomes AF: 0.0544 AC: 8271 AN: 152140 Hom.: 727 Cov.: 32

Gnomad AFR AF: 0.0416

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.198

Gnomad ASJ AF: 0.0242

Gnomad EAS AF: 0.330

Gnomad SAS AF: 0.0401

Gnomad FIN AF: 0.0434

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0135

Gnomad OTH AF: 0.0636

GnomAD4 exome AF: 0.0509 AC: 19255 AN: 377996 Hom.: 2189 Cov.: 4 AF XY: 0.0489 AC XY: 9618 AN XY: 196818

Gnomad4 AFR exome AF: 0.0392

Gnomad4 AMR exome AF: 0.242

Gnomad4 ASJ exome AF: 0.0245

Gnomad4 EAS exome AF: 0.349

Gnomad4 SAS exome AF: 0.0277

Gnomad4 FIN exome AF: 0.0436

Gnomad4 NFE exome AF: 0.0130

Gnomad4 OTH exome AF: 0.0501

GnomAD4 genome AF: 0.0545 AC: 8301 AN: 152258 Hom.: 738 Cov.: 32 AF XY: 0.0589 AC XY: 4382 AN XY: 74454

Gnomad4 AFR AF: 0.0417

Gnomad4 AMR AF: 0.199

Gnomad4 ASJ AF: 0.0242

Gnomad4 EAS AF: 0.330

Gnomad4 SAS AF: 0.0400

Gnomad4 FIN AF: 0.0434

Gnomad4 NFE AF: 0.0135

Gnomad4 OTH AF: 0.0653

Alfa AF: 0.00675 Hom.: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.1
DANN	Benign	0.42

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;