1-54039764-C-A

Variant names:

• chr1-54039764-C-A
• rs3766466
• NM_004872.5:c.707+992G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004872.5(TMEM59):​c.707+992G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 151,672 control chromosomes in the GnomAD database, including 2,948 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 0.13 (2948 hom., cov: 32)
• Consequence: TMEM59 NM_004872.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0990
• Publications: 5 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.366 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004872.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM59	NM_004872.5	MANE Select	c.707+992G>T		intron	N/A	NP_004863.2
	TMEM59	NM_001305043.2		c.710+992G>T		intron	N/A	NP_001291972.1
	TMEM59	NM_001305050.2		c.509+992G>T		intron	N/A	NP_001291979.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM59	ENST00000234831.10	TSL:1 MANE Select	c.707+992G>T		intron	N/A	ENSP00000234831.5	Q9BXS4
	TMEM59	ENST00000371348.5	TSL:1	c.314+992G>T		intron	N/A	ENSP00000360399.1	Q5T6Z8
	TMEM59	ENST00000864587.1		c.710+992G>T		intron	N/A	ENSP00000534646.1

Frequencies

GnomAD3 genomes AF: 0.129 AC: 19610 AN: 151554 Hom.: 2941 Cov.: 32

Gnomad AFR AF: 0.371

Gnomad AMI AF: 0.0318

Gnomad AMR AF: 0.0614

Gnomad ASJ AF: 0.0938

Gnomad EAS AF: 0.0433

Gnomad SAS AF: 0.0496

Gnomad FIN AF: 0.0305

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.0294

Gnomad OTH AF: 0.110

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.130 AC: 19648 AN: 151672 Hom.: 2948 Cov.: 32 AF XY: 0.128 AC XY: 9495 AN XY: 74102

African (AFR) AF: 0.371 AC: 15319 AN: 41264

American (AMR) AF: 0.0612 AC: 933 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.0938 AC: 325 AN: 3466

East Asian (EAS) AF: 0.0424 AC: 219 AN: 5164

South Asian (SAS) AF: 0.0497 AC: 239 AN: 4812

European-Finnish (FIN) AF: 0.0305 AC: 319 AN: 10460

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.0294 AC: 1999 AN: 67954

Other (OTH) AF: 0.110 AC: 231 AN: 2108

Alfa AF: 0.0571 Hom.: 3539

Bravo AF: 0.142

Asia WGS AF: 0.0780 AC: 270 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.6
DANN	Benign	0.63
PhyloP100		0.099
Mutation Taster		=100/0	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: rs3766466; hg19: chr1-54505437;