Genetic Variant TMEM87A:c.869-59G>A (chr15-42236478-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_015497.5(TMEM87A):c.869-59G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.748 in 1,398,526 control chromosomes in the GnomAD database, including 408,524 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 0.60 ( 33011 hom., cov: 32)

Exomes 𝑓: 0.77 ( 375513 hom. )

Consequence

TMEM87A
NM_015497.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.704

Publications

19 publications found

Variant links:

Genes affected

TMEM87A (HGNC:24522): (transmembrane protein 87A) Involved in retrograde transport, endosome to Golgi. Located in Golgi cisterna membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM87A links:

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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=-0.87).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.798 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015497.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
TMEM87A	NM_015497.5	MANE Select	c.869-59G>A	intron	N/A	NP_056312.2
TMEM87A	NM_001438982.1		c.869-59G>A	intron	N/A	NP_001425911.1
TMEM87A	NM_001438983.1		c.869-59G>A	intron	N/A	NP_001425912.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TMEM87A	ENST00000389834.9	TSL:2 MANE Select	c.869-59G>A	intron	N/A	ENSP00000374484.4	Q8NBN3-1
TMEM87A	ENST00000566014.2	TSL:5	c.869-59G>A	intron	N/A	ENSP00000457308.2	H3BTS6
TMEM87A	ENST00000704760.1		c.869-59G>A	intron	N/A	ENSP00000516026.1	A0A994J4W5

Frequencies

GnomAD3 genomes

AF:

0.596

AC:

90557

AN:

151952

Hom.:

33021

Cov.:

show subpopulations

Gnomad AFR

AF:

0.158

Gnomad AMI

AF:

0.885

Gnomad AMR

AF:

0.577

Gnomad ASJ

AF:

0.710

Gnomad EAS

AF:

0.813

Gnomad SAS

AF:

0.667

Gnomad FIN

AF:

0.781

Gnomad MID

AF:

0.769

Gnomad NFE

AF:

0.804

Gnomad OTH

AF:

0.641

GnomAD4 exome

AF:

0.766

AC:

955099

AN:

1246456

Hom.:

375513

AF XY:

0.767

AC XY:

483710

AN XY:

630690

show subpopulations

African (AFR)

AF:

0.139

AC:

4020

AN:

29008

American (AMR)

AF:

0.490

AC:

21645

AN:

44168

Ashkenazi Jewish (ASJ)

AF:

0.734

AC:

18077

AN:

24622

East Asian (EAS)

AF:

0.831

AC:

31985

AN:

38494

South Asian (SAS)

AF:

0.673

AC:

55008

AN:

81730

European-Finnish (FIN)

AF:

0.790

AC:

41446

AN:

52442

Middle Eastern (MID)

AF:

0.729

AC:

3890

AN:

5334

European-Non Finnish (NFE)

AF:

0.806

AC:

739941

AN:

917498

Other (OTH)

AF:

0.735

AC:

39087

AN:

53160

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

9958

19917

29875

39834

49792

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15654

31308

46962

62616

78270

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.595

AC:

90537

AN:

152070

Hom.:

33011

Cov.:

AF XY:

0.597

AC XY:

44385

AN XY:

74362

show subpopulations

African (AFR)

AF:

0.158

AC:

6533

AN:

41458

American (AMR)

AF:

0.576

AC:

8793

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.710

AC:

2460

AN:

3466

East Asian (EAS)

AF:

0.813

AC:

4197

AN:

5164

South Asian (SAS)

AF:

0.667

AC:

3215

AN:

4820

European-Finnish (FIN)

AF:

0.781

AC:

8265

AN:

10580

Middle Eastern (MID)

AF:

0.755

AC:

222

AN:

294

European-Non Finnish (NFE)

AF:

0.804

AC:

54683

AN:

68002

Other (OTH)

AF:

0.645

AC:

1362

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1279

2558

3837

5116

6395

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

704

1408

2112

2816

3520

<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:

0.708

Hom.:

94430

Bravo

AF:

0.561

Asia WGS

AF:

0.699

AC:

2432

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.52

(source)

DANN

Benign

0.29

PhyloP100

-0.70

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over