1-54053434-G-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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]

TCEANC2 (HGNC:26494): (transcription elongation factor A N-terminal and central domain containing 2) Predicted to be involved in transcription, DNA-templated. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001305049.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

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

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM59	ENST00000371341.5	TSL:2	c.-283C>G		5_prime_UTR	Exon 1 of 8	ENSP00000360392.1
	TMEM59	ENST00000440019.5	TSL:2	c.-177C>G		5_prime_UTR	Exon 1 of 6	ENSP00000399761.1
	TMEM59	ENST00000234831.10	TSL:1 MANE Select	c.-246C>G		upstream_gene	N/A	ENSP00000234831.5

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

African (AFR) AF: 0.0392 AC: 430 AN: 10974

American (AMR) AF: 0.242 AC: 3296 AN: 13634

Ashkenazi Jewish (ASJ) AF: 0.0245 AC: 294 AN: 12004

East Asian (EAS) AF: 0.349 AC: 9009 AN: 25778

South Asian (SAS) AF: 0.0277 AC: 957 AN: 34598

European-Finnish (FIN) AF: 0.0436 AC: 1125 AN: 25816

Middle Eastern (MID) AF: 0.00697 AC: 12 AN: 1722

European-Non Finnish (NFE) AF: 0.0130 AC: 3007 AN: 230996

Other (OTH) AF: 0.0501 AC: 1125 AN: 22474

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

African (AFR) AF: 0.0417 AC: 1731 AN: 41524

American (AMR) AF: 0.199 AC: 3049 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0242 AC: 84 AN: 3468

East Asian (EAS) AF: 0.330 AC: 1705 AN: 5166

South Asian (SAS) AF: 0.0400 AC: 193 AN: 4828

European-Finnish (FIN) AF: 0.0434 AC: 461 AN: 10626

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0135 AC: 918 AN: 68026

Other (OTH) AF: 0.0653 AC: 138 AN: 2114

Alfa AF: 0.00643 Hom.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.1
DANN	Benign	0.42
PhyloP100		-1.8
PromoterAI		-0.12	Neutral
Mutation Taster		=299/1	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: rs2236512; hg19: chr1-54519107;