Variant 15-42260968-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_015497.5(TMEM87A):c.494G>A(p.Gly165Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000311 in 1,608,504 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

TMEM87A
NM_015497.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.624

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:

TMEM87A (HGNC:):

TMEM87A links:

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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=0.108308405).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM87A	NM_015497.5 linkuse as main transcript	c.494G>A	p.Gly165Glu	missense_variant	6/20	ENST00000389834.9	NP_056312.2	Q8NBN3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TMEM87A	ENST00000389834.9 linkuse as main transcript	c.494G>A	p.Gly165Glu	missense_variant	6/20	2	NM_015497.5	ENSP00000374484.4	Q8NBN3-1
TMEM87A	ENST00000566014.2 linkuse as main transcript	c.494G>A	p.Gly165Glu	missense_variant	6/20	5		ENSP00000457308.2	H3BTS6
TMEM87A	ENST00000704760.1 linkuse as main transcript	c.494G>A	p.Gly165Glu	missense_variant	6/20			ENSP00000516026.1	A0A994J4W5
TMEM87A	ENST00000704761.1 linkuse as main transcript	c.494G>A	p.Gly165Glu	missense_variant	6/20			ENSP00000516027.1	A0A994J7M5
TMEM87A	ENST00000448392.6 linkuse as main transcript	n.*259G>A		non_coding_transcript_exon_variant	5/19	1		ENSP00000405379.2	H3BRG0
TMEM87A	ENST00000448392.6 linkuse as main transcript	n.*259G>A		3_prime_UTR_variant	5/19	1		ENSP00000405379.2	H3BRG0

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

151974

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000657

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000121

AC:

AN:

247568

Hom.:

AF XY:

0.00000747

AC XY:

AN XY:

133926

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000894

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000275

AC:

AN:

1456530

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

724532

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000681

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:

9.01e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000658

AC:

AN:

151974

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74202

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000657

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 21, 2024

The c.494G>A (p.G165E) alteration is located in exon 6 (coding exon 6) of the TMEM87A gene. This alteration results from a G to A substitution at nucleotide position 494, causing the glycine (G) at amino acid position 165 to be replaced by a glutamic acid (E). 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

Benign

0.085

BayesDel_addAF

Benign

-0.0085

BayesDel_noAF

Uncertain

-0.050

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.018

.;T;T;.;.;T;.;.

Eigen

Benign

-0.0023

Eigen_PC

Benign

0.11

FATHMM_MKL

Benign

0.59

LIST_S2

Benign

0.76

T;T;T;T;T;T;T;T

M_CAP

Benign

0.0017

MetaRNN

Benign

0.11

T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.7

.;L;.;.;.;.;L;.

PrimateAI

Uncertain

0.49

PROVEAN

Benign

0.21

N;N;N;N;D;D;N;D

REVEL

Benign

0.12

Sift

Benign

0.81

T;T;T;T;T;D;T;D

Sift4G

Benign

1.0

T;T;T;.;.;D;T;D

Polyphen

0.0020

B;B;.;.;.;.;D;.

Vest4

0.26

MutPred

0.42

.;Gain of loop (P = 0.024);.;.;.;.;Gain of loop (P = 0.024);.;

MVP

0.082

MPC

0.34

ClinPred

0.20

GERP RS

3.6

Varity_R

0.030

gMVP

0.65

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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