1-54034512-A-G

Position:

• chr1-54034512-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004872.5(TMEM59):​c.816+2098T>C 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 152,092 control chromosomes in the GnomAD database, including 2,954 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 (2953 hom., cov: 31)
  • Exomes 𝑓: 0.038 (1 hom.)
• Consequence: TMEM59 NM_004872.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.49

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]

ENSG00000280378 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.366 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM59	NM_004872.5	c.816+2098T>C		intron_variant		ENST00000234831.10	NP_004863.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM59	ENST00000234831.10	c.816+2098T>C		intron_variant		1	NM_004872.5	ENSP00000234831.5

Frequencies

GnomAD3 genomes AF: 0.130 AC: 19675 AN: 151844 Hom.: 2947 Cov.: 31

Gnomad AFR AF: 0.371

Gnomad AMI AF: 0.0318

Gnomad AMR AF: 0.0616

Gnomad ASJ AF: 0.0942

Gnomad EAS AF: 0.0432

Gnomad SAS AF: 0.0499

Gnomad FIN AF: 0.0303

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.0295

Gnomad OTH AF: 0.111

GnomAD4 exome AF: 0.0385 AC: 5 AN: 130 Hom.: 1 Cov.: 0 AF XY: 0.0385 AC XY: 4 AN XY: 104

Gnomad4 AFR exome AF: 0.750

Gnomad4 EAS exome AF: 0.500

Gnomad4 SAS exome AF: 0.00

Gnomad4 NFE exome AF: 0.00862

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.130 AC: 19710 AN: 151962 Hom.: 2953 Cov.: 31 AF XY: 0.128 AC XY: 9522 AN XY: 74324

Gnomad4 AFR AF: 0.371

Gnomad4 AMR AF: 0.0615

Gnomad4 ASJ AF: 0.0942

Gnomad4 EAS AF: 0.0423

Gnomad4 SAS AF: 0.0500

Gnomad4 FIN AF: 0.0303

Gnomad4 NFE AF: 0.0295

Gnomad4 OTH AF: 0.110

Alfa AF: 0.0914 Hom.: 246

Bravo AF: 0.143

Asia WGS AF: 0.0760 AC: 265 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.76
DANN	Benign	0.28

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: rs7528837; hg19: chr1-54500185;