rs2236512

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

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

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>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
• 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.303 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>T		5_prime_UTR	Exon 1 of 8	NP_001291978.1
	TMEM59	NM_001305051.1		c.-283C>T		5_prime_UTR	Exon 1 of 8	NP_001291980.1
	TMEM59	NM_001305052.1		c.-177C>T		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>T		5_prime_UTR	Exon 1 of 8	ENSP00000360392.1
	TMEM59	ENST00000440019.5	TSL:2	c.-177C>T		5_prime_UTR	Exon 1 of 6	ENSP00000399761.1
	TMEM59	ENST00000234831.10	TSL:1 MANE Select	c.-246C>T		upstream_gene	N/A	ENSP00000234831.5

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

African (AFR) AF: 0.304 AC: 3328 AN: 10954

American (AMR) AF: 0.0310 AC: 425 AN: 13688

Ashkenazi Jewish (ASJ) AF: 0.0270 AC: 324 AN: 12004

East Asian (EAS) AF: 0.0336 AC: 869 AN: 25834

South Asian (SAS) AF: 0.0450 AC: 1557 AN: 34602

European-Finnish (FIN) AF: 0.0261 AC: 673 AN: 25824

Middle Eastern (MID) AF: 0.0557 AC: 96 AN: 1722

European-Non Finnish (NFE) AF: 0.0237 AC: 5471 AN: 230964

Other (OTH) AF: 0.0512 AC: 1151 AN: 22474

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

African (AFR) AF: 0.308 AC: 12783 AN: 41508

American (AMR) AF: 0.0431 AC: 660 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0285 AC: 99 AN: 3470

East Asian (EAS) AF: 0.0399 AC: 206 AN: 5168

South Asian (SAS) AF: 0.0477 AC: 230 AN: 4824

European-Finnish (FIN) AF: 0.0300 AC: 319 AN: 10622

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0240 AC: 1633 AN: 68024

Other (OTH) AF: 0.0823 AC: 174 AN: 2114

Alfa AF: 0.0195 Hom.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.5
DANN	Benign	0.87
PhyloP100		-1.8
PromoterAI		-0.11	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;