dbSNP rs7528837: TMEM59:c.816+2098T>C (chr1-54034512-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.49

Publications

3 publications found

Variant links:

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]

TMEM59 links:

ENSG00000280378 (HGNC:):

ENSG00000280378 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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.

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
TMEM59	NM_004872.5	MANE Select	c.816+2098T>C	intron	N/A	NP_004863.2
TMEM59	NM_001305043.2		c.819+2098T>C	intron	N/A	NP_001291972.1
TMEM59	NM_001305050.2		c.618+2098T>C	intron	N/A	NP_001291979.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TMEM59	ENST00000234831.10	TSL:1 MANE Select	c.816+2098T>C	intron	N/A	ENSP00000234831.5	Q9BXS4
TMEM59	ENST00000371348.5	TSL:1	c.423+2098T>C	intron	N/A	ENSP00000360399.1	Q5T6Z8
TMEM59	ENST00000864587.1		c.936+2098T>C	intron	N/A	ENSP00000534646.1

Frequencies

GnomAD3 genomes

AF:

0.130

AC:

19675

AN:

151844

Hom.:

2947

Cov.:

show subpopulations

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:

AN:

130

Hom.:

Cov.:

AF XY:

0.0385

AC XY:

AN XY:

104

show subpopulations

African (AFR)

AF:

0.750

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.500

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00862

AC:

AN:

116

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.130

AC:

19710

AN:

151962

Hom.:

2953

Cov.:

AF XY:

0.128

AC XY:

9522

AN XY:

74324

show subpopulations

African (AFR)

AF:

0.371

AC:

15365

AN:

41424

American (AMR)

AF:

0.0615

AC:

939

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.0942

AC:

326

AN:

3462

East Asian (EAS)

AF:

0.0423

AC:

218

AN:

5152

South Asian (SAS)

AF:

0.0500

AC:

240

AN:

4802

European-Finnish (FIN)

AF:

0.0303

AC:

322

AN:

10620

Middle Eastern (MID)

AF:

0.119

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0295

AC:

2003

AN:

67912

Other (OTH)

AF:

0.110

AC:

233

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

717

1435

2152

2870

3587

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

178

356

534

712

890

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.102

Hom.:

295

Bravo

AF:

0.143

Asia WGS

AF:

0.0760

AC:

265

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.76

(source)

DANN

Benign

0.28

PhyloP100

-1.5

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over