15-42211714-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_015497.5(TMEM87A):​c.1662G>A​(p.Met554Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

TMEM87A
NM_015497.5 missense

Scores

4
11
4

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.41
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]
VPS39-DT (HGNC:55378): (VPS39 divergent transcript)

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TMEM87ANM_015497.5 linkc.1662G>A p.Met554Ile missense_variant Exon 20 of 20 ENST00000389834.9 NP_056312.2 Q8NBN3-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TMEM87AENST00000389834.9 linkc.1662G>A p.Met554Ile missense_variant Exon 20 of 20 2 NM_015497.5 ENSP00000374484.4 Q8NBN3-1
TMEM87AENST00000566014.2 linkc.1665G>A p.Met555Ile missense_variant Exon 20 of 20 5 ENSP00000457308.2 H3BTS6
TMEM87AENST00000704760.1 linkc.1659G>A p.Met553Ile missense_variant Exon 20 of 20 ENSP00000516026.1 A0A994J4W5
TMEM87AENST00000704761.1 linkc.1659G>A p.Met553Ile missense_variant Exon 20 of 20 ENSP00000516027.1 A0A994J7M5
TMEM87AENST00000448392.6 linkn.*1427G>A non_coding_transcript_exon_variant Exon 19 of 19 1 ENSP00000405379.2 H3BRG0
TMEM87AENST00000448392.6 linkn.*1427G>A 3_prime_UTR_variant Exon 19 of 19 1 ENSP00000405379.2 H3BRG0

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
29
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Aug 13, 2021
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1662G>A (p.M554I) alteration is located in exon 20 (coding exon 20) of the TMEM87A gene. This alteration results from a G to A substitution at nucleotide position 1662, causing the methionine (M) at amino acid position 554 to be replaced by an isoleucine (I). 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
0.94
BayesDel_addAF
Pathogenic
0.19
D
BayesDel_noAF
Uncertain
0.030
CADD
Uncertain
26
DANN
Uncertain
0.99
DEOGEN2
Benign
0.22
.;T
Eigen
Uncertain
0.64
Eigen_PC
Uncertain
0.66
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.87
D;D
M_CAP
Benign
0.0081
T
MetaRNN
Uncertain
0.50
T;T
MetaSVM
Benign
-0.56
T
MutationAssessor
Uncertain
2.4
.;M
PrimateAI
Pathogenic
0.83
D
PROVEAN
Uncertain
-3.0
D;D
REVEL
Uncertain
0.39
Sift
Uncertain
0.029
D;D
Sift4G
Uncertain
0.042
D;D
Polyphen
0.98
.;D
Vest4
0.66
MutPred
0.25
.;Loss of disorder (P = 0.1459);
MVP
0.24
MPC
0.98
ClinPred
0.96
D
GERP RS
5.3
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.46
gMVP
0.22

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.

Other links and lift over

dbSNP: rs2050290814; hg19: chr15-42503912; API