15-42226908-T-C

Variant names:

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_015497.5(TMEM87A):c.1301A>G(p.Asp434Gly) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.000105 in 1,613,724 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

TMEM87A
NM_015497.5 missense, splice_region

Scores

Splicing: ADA: 0.4777

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.92

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:

VPS39-DT (HGNC:55378): (VPS39 divergent transcript)

VPS39-DT links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.21770036).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM87A	NM_015497.5 link	c.1301A>G	p.Asp434Gly	missense_variant, splice_region_variant	Exon 15 of 20	ENST00000389834.9	NP_056312.2	Q8NBN3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TMEM87A	ENST00000389834.9 link	c.1301A>G	p.Asp434Gly	missense_variant, splice_region_variant	Exon 15 of 20	2	NM_015497.5	ENSP00000374484.4	Q8NBN3-1
TMEM87A	ENST00000566014.2 link	c.1304A>G	p.Asp435Gly	missense_variant, splice_region_variant	Exon 15 of 20	5		ENSP00000457308.2	H3BTS6
TMEM87A	ENST00000704760.1 link	c.1301A>G	p.Asp434Gly	missense_variant, splice_region_variant	Exon 15 of 20			ENSP00000516026.1	A0A994J4W5
TMEM87A	ENST00000704761.1 link	c.1301A>G	p.Asp434Gly	missense_variant, splice_region_variant	Exon 15 of 20			ENSP00000516027.1	A0A994J7M5
TMEM87A	ENST00000448392.6 link	n.*1066A>G		splice_region_variant, non_coding_transcript_exon_variant	Exon 14 of 19	1		ENSP00000405379.2	H3BRG0
TMEM87A	ENST00000448392.6 link	n.*1066A>G		3_prime_UTR_variant	Exon 14 of 19	1		ENSP00000405379.2	H3BRG0

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000677

AC:

AN:

251112

Hom.:

AF XY:

0.0000884

AC XY:

AN XY:

135716

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000173

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000792

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000111

AC:

162

AN:

1461518

Hom.:

Cov.:

AF XY:

0.0000853

AC XY:

AN XY:

727074

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000134

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000132

Gnomad4 OTH exome

AF:

0.000149

GnomAD4 genome

AF:

0.0000526

AC:

AN:

152206

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000155

Hom.:

Bravo

AF:

0.0000604

ExAC

AF:

0.0000330

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 21, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1301A>G (p.D434G) alteration is located in exon 15 (coding exon 15) of the TMEM87A gene. This alteration results from a A to G substitution at nucleotide position 1301, causing the aspartic acid (D) at amino acid position 434 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.81

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.23

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.24

.;T

Eigen

Benign

0.13

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Uncertain

0.80

LIST_S2

Uncertain

0.90

D;D

M_CAP

Benign

0.0051

MetaRNN

Benign

0.22

T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.7

.;L

PrimateAI

Uncertain

0.69

PROVEAN

Pathogenic

-4.5

D;D

REVEL

Benign

0.17

Sift

Benign

0.17

T;T

Sift4G

Benign

0.27

T;T

Polyphen

0.64

.;P

Vest4

0.32

MVP

0.093

MPC

0.84

ClinPred

0.27

GERP RS

5.2

Varity_R

0.38

gMVP

0.82

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.48

dbscSNV1_RF

Benign

0.38

SpliceAI score (max)

0.050

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over