chr15-42211714-C-T

Variant names:

• chr15-42211714-C-T
• rs2050290814
• NM_015497.5:c.1662G>A

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.41
• Publications: 0 publications found

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)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM87A	NM_015497.5	MANE Select	c.1662G>A	p.Met554Ile	missense	Exon 20 of 20	NP_056312.2
	TMEM87A	NM_001438982.1		c.1665G>A	p.Met555Ile	missense	Exon 20 of 20	NP_001425911.1
	TMEM87A	NM_001438983.1		c.1662G>A	p.Met554Ile	missense	Exon 20 of 20	NP_001425912.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM87A	ENST00000389834.9	TSL:2 MANE Select	c.1662G>A	p.Met554Ile	missense	Exon 20 of 20	ENSP00000374484.4	Q8NBN3-1
	TMEM87A	ENST00000566014.2	TSL:5	c.1665G>A	p.Met555Ile	missense	Exon 20 of 20	ENSP00000457308.2	H3BTS6
	TMEM87A	ENST00000704760.1		c.1659G>A	p.Met553Ile	missense	Exon 20 of 20	ENSP00000516026.1	A0A994J4W5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.0081	T
MetaRNN	Uncertain	0.50	T
MetaSVM	Benign	-0.56	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		5.4
PrimateAI	Pathogenic	0.83	D
PROVEAN	Uncertain	-3.0	D
REVEL	Uncertain	0.39
Sift	Uncertain	0.029	D
Sift4G	Uncertain	0.042	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

Other links and lift over

dbSNP: rs2050290814; hg19: chr15-42503912;