15-42228739-T-G

Position:

• chr15-42228739-T-G

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_015497.5(TMEM87A):​c.1213A>C​(p.Thr405Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TMEM87A NM_015497.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.83

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 (HGNC:):

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.967

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM87A	NM_015497.5	c.1213A>C	p.Thr405Pro	missense_variant	13/20	ENST00000389834.9	NP_056312.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM87A	ENST00000389834.9	c.1213A>C	p.Thr405Pro	missense_variant	13/20	2	NM_015497.5	ENSP00000374484.4
TMEM87A	ENST00000566014.2	c.1216A>C	p.Thr406Pro	missense_variant	13/20	5		ENSP00000457308.2
TMEM87A	ENST00000704760.1	c.1213A>C	p.Thr405Pro	missense_variant	13/20			ENSP00000516026.1
TMEM87A	ENST00000704761.1	c.1213A>C	p.Thr405Pro	missense_variant	13/20			ENSP00000516027.1
TMEM87A	ENST00000448392.6	n.*978A>C		non_coding_transcript_exon_variant	12/19	1		ENSP00000405379.2
TMEM87A	ENST00000448392.6	n.*978A>C		3_prime_UTR_variant	12/19	1		ENSP00000405379.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 25, 2024

The c.1213A>C (p.T405P) alteration is located in exon 13 (coding exon 13) of the TMEM87A gene. This alteration results from a A to C substitution at nucleotide position 1213, causing the threonine (T) at amino acid position 405 to be replaced by a proline (P). 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	0.96
BayesDel_addAF	Pathogenic	0.48	D
BayesDel_noAF	Pathogenic	0.46
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.56	.;D
Eigen	Pathogenic	0.83
Eigen_PC	Pathogenic	0.79
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.90	D;D
M_CAP	Benign	0.045	D
MetaRNN	Pathogenic	0.97	D;D
MetaSVM	Uncertain	-0.10	T
MutationAssessor	Pathogenic	3.0	.;M
PrimateAI	Uncertain	0.72	T
PROVEAN	Pathogenic	-5.5	D;D
REVEL	Pathogenic	0.73
Sift	Uncertain	0.0020	D;D
Sift4G	Uncertain	0.0020	D;D
Polyphen		1.0	.;D
Vest4		0.74
MutPred		0.90		.;Loss of MoRF binding (P = 0.0677);
MVP		0.44
MPC		1.1
ClinPred		1.0	D
GERP RS		5.4
Varity_R		0.92
gMVP		0.96

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.21		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.21		Position offset: -27

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-42520937;