1-54032127-C-T

Variant names:

• chr1-54032127-C-T
• rs776119905
• NM_004872.5:c.*23G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004872.5(TMEM59):​c.*23G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as risk factor (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TMEM59 NM_004872.5 3_prime_UTR
• Clinical Significance: risk factor no assertion criteria provided O:1
• Conservation: PhyloP100: -0.0190
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).

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.*23G>A		3_prime_UTR	Exon 8 of 8	NP_004863.2
	TMEM59	NM_001305043.2		c.*23G>A		3_prime_UTR	Exon 8 of 8	NP_001291972.1
	TMEM59	NM_001305050.2		c.*23G>A		3_prime_UTR	Exon 6 of 6	NP_001291979.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM59	ENST00000234831.10	TSL:1 MANE Select	c.*23G>A		3_prime_UTR	Exon 8 of 8	ENSP00000234831.5	Q9BXS4
	TMEM59	ENST00000371348.5	TSL:1	c.*23G>A		3_prime_UTR	Exon 7 of 7	ENSP00000360399.1	Q5T6Z8
	TMEM59	ENST00000864587.1		c.*23G>A		3_prime_UTR	Exon 9 of 9	ENSP00000534646.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: risk factor

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	-	Estrogen resistance syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	8.1
DANN	Benign	0.59
PhyloP100		-0.019

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: rs776119905; hg19: chr1-54497800;