1-54053434-G-T

Variant names:

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

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001305049.1(TMEM59):​c.-283C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000032 in 530,466 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000042 (0 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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM59	NM_001305049.1	c.-283C>A		5_prime_UTR_variant	Exon 1 of 8		NP_001291978.1
TMEM59	NM_001305051.1	c.-283C>A		5_prime_UTR_variant	Exon 1 of 8		NP_001291980.1
TMEM59	NM_001305052.1	c.-177C>A		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>A		5_prime_UTR_variant	Exon 1 of 8	2		ENSP00000360392.1
TMEM59	ENST00000440019.5	c.-177C>A		5_prime_UTR_variant	Exon 1 of 6	2		ENSP00000399761.1
TMEM59	ENST00000452421.5	c.-246C>A		upstream_gene_variant		5		ENSP00000397772.1
TMEM59	ENST00000420738.5	c.-316C>A		upstream_gene_variant		3		ENSP00000413792.1

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152146 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000423 AC: 16 AN: 378202 Hom.: 0 Cov.: 4 AF XY: 0.0000660 AC XY: 13 AN XY: 196916

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000730

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000387

Gnomad4 SAS exome AF: 0.0000867

Gnomad4 FIN exome AF: 0.0000387

Gnomad4 NFE exome AF: 0.0000390

Gnomad4 OTH exome AF: 0.0000445

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152264 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74458

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.0
DANN	Benign	0.59

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;