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

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM59	NM_004872.5	c.-246C>T		upstream_gene_variant		ENST00000234831.10	NP_004863.2
TCEANC2	NM_153035.3	c.-367G>A		upstream_gene_variant		ENST00000234827.6	NP_694580.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM59	ENST00000234831.10	c.-246C>T		upstream_gene_variant		1	NM_004872.5	ENSP00000234831.5
TCEANC2	ENST00000234827.6	c.-367G>A		upstream_gene_variant		1	NM_153035.3	ENSP00000234827.1

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 AC: 3328 AN: 10954

Gnomad4 AMR exome AF: 0.0310 AC: 425 AN: 13688

Gnomad4 ASJ exome AF: 0.0270 AC: 324 AN: 12004

Gnomad4 EAS exome AF: 0.0336 AC: 869 AN: 25834

Gnomad4 SAS exome AF: 0.0450 AC: 1557 AN: 34602

Gnomad4 FIN exome AF: 0.0261 AC: 673 AN: 25824

Gnomad4 NFE exome AF: 0.0237 AC: 5471 AN: 230964

Gnomad4 Remaining exome 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

Gnomad4 AFR AF: 0.308 AC: 0.307965 AN: 0.307965

Gnomad4 AMR AF: 0.0431 AC: 0.0431429 AN: 0.0431429

Gnomad4 ASJ AF: 0.0285 AC: 0.0285303 AN: 0.0285303

Gnomad4 EAS AF: 0.0399 AC: 0.0398607 AN: 0.0398607

Gnomad4 SAS AF: 0.0477 AC: 0.0476783 AN: 0.0476783

Gnomad4 FIN AF: 0.0300 AC: 0.030032 AN: 0.030032

Gnomad4 NFE AF: 0.0240 AC: 0.0240062 AN: 0.0240062

Gnomad4 OTH AF: 0.0823 AC: 0.0823084 AN: 0.0823084

Alfa AF: 0.0195 Hom.: 34

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
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

Publications

LitVar

Other links and lift over

dbSNP: rs2236512; hg19: chr1-54519107;