Genetic Variant NM_015497.5: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:

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=-0.87).

BA1

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM87A	NM_015497.5 link	c.869-59G>A		intron_variant	Intron 9 of 19	ENST00000389834.9	NP_056312.2	Q8NBN3-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
TMEM87A	ENST00000389834.9 link	c.869-59G>A	intron_variant	Intron 9 of 19	2	NM_015497.5	ENSP00000374484.4	Q8NBN3-1
TMEM87A	ENST00000566014.2 link	c.869-59G>A	intron_variant	Intron 9 of 19	5		ENSP00000457308.2	H3BTS6
TMEM87A	ENST00000704760.1 link	c.869-59G>A	intron_variant	Intron 9 of 19			ENSP00000516026.1	A0A994J4W5
TMEM87A	ENST00000704761.1 link	c.869-59G>A	intron_variant	Intron 9 of 19			ENSP00000516027.1	A0A994J7M5
TMEM87A	ENST00000448392.6 link	n.*634-59G>A	intron_variant	Intron 8 of 18	1		ENSP00000405379.2	H3BRG0

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 v4.3

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over