chr1-54048154-T-A

Variant names:

• chr1-54048154-T-A
• rs914722
• NM_004872.5:c.190-782A>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.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
• Publications: 2 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.43 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.190-782A>T		intron	N/A	NP_004863.2
	TMEM59	NM_001305043.2		c.190-782A>T		intron	N/A	NP_001291972.1
	TMEM59	NM_001305050.2		c.190-4629A>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.190-782A>T		intron	N/A	ENSP00000234831.5	Q9BXS4
	TMEM59	ENST00000864587.1		c.190-782A>T		intron	N/A	ENSP00000534646.1
	TMEM59	ENST00000864584.1		c.190-782A>T		intron	N/A	ENSP00000534643.1

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.00 AC: 0 AN: 2

European-Finnish (FIN) AF: 0.500 AC: 1 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.313 AC: 5 AN: 16

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.260 AC: 10795 AN: 41444

American (AMR) AF: 0.439 AC: 6698 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.345 AC: 1195 AN: 3464

East Asian (EAS) AF: 0.358 AC: 1854 AN: 5174

South Asian (SAS) AF: 0.234 AC: 1131 AN: 4824

European-Finnish (FIN) AF: 0.235 AC: 2473 AN: 10540

Middle Eastern (MID) AF: 0.395 AC: 116 AN: 294

European-Non Finnish (NFE) AF: 0.327 AC: 22255 AN: 67966

Other (OTH) AF: 0.378 AC: 798 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.28
DANN	Benign	0.74
PhyloP100		-2.3
PromoterAI		0.0068	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs914722; hg19: chr1-54513827;