rs914722

Positions:

• chr1-54048154-T-A
• chr1-54048154-T-C

Variant summary

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

The NM_004872.5(TMEM59):​c.190-782A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.313 in 152,014 control chromosomes in the GnomAD database, including 7,780 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 0.31 (7778 hom., cov: 32)
  • Exomes 𝑓: 0.30 (2 hom.)
• Consequence: TMEM59 NM_004872.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.29

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.43 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM59	NM_004872.5	c.190-782A>T		intron_variant		ENST00000234831.10	NP_004863.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM59	ENST00000234831.10	c.190-782A>T		intron_variant		1	NM_004872.5	ENSP00000234831.5

Frequencies

GnomAD3 genomes AF: 0.313 AC: 47606 AN: 151878 Hom.: 7763 Cov.: 32

Gnomad AFR AF: 0.260

Gnomad AMI AF: 0.367

Gnomad AMR AF: 0.438

Gnomad ASJ AF: 0.345

Gnomad EAS AF: 0.358

Gnomad SAS AF: 0.235

Gnomad FIN AF: 0.235

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.327

Gnomad OTH AF: 0.379

GnomAD4 exome AF: 0.300 AC: 6 AN: 20 Hom.: 2 AF XY: 0.417 AC XY: 5 AN XY: 12

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.313

GnomAD4 genome AF: 0.313 AC: 47649 AN: 151994 Hom.: 7778 Cov.: 32 AF XY: 0.310 AC XY: 23046 AN XY: 74278

Gnomad4 AFR AF: 0.260

Gnomad4 AMR AF: 0.439

Gnomad4 ASJ AF: 0.345

Gnomad4 EAS AF: 0.358

Gnomad4 SAS AF: 0.234

Gnomad4 FIN AF: 0.235

Gnomad4 NFE AF: 0.327

Gnomad4 OTH AF: 0.378

Alfa AF: 0.116 Hom.: 168

Bravo AF: 0.332

Asia WGS AF: 0.298 AC: 1040 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.28
DANN	Benign	0.74

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs914722; hg19: chr1-54513827;