NM_015497.5:c.1514A>T

Variant names:

• chr15-42219606-T-A
• rs375405837
• NM_015497.5:c.1514A>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_015497.5(TMEM87A):​c.1514A>T​(p.Asn505Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000138 in 1,448,428 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N505S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: TMEM87A NM_015497.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.49
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30257612).

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.1514A>T	p.Asn505Ile	missense	Exon 17 of 20	NP_056312.2
	TMEM87A	NM_001438982.1		c.1517A>T	p.Asn506Ile	missense	Exon 17 of 20	NP_001425911.1
	TMEM87A	NM_001438983.1		c.1517A>T	p.Asn506Ile	missense	Exon 17 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.1514A>T	p.Asn505Ile	missense	Exon 17 of 20	ENSP00000374484.4	Q8NBN3-1
	TMEM87A	ENST00000566014.2	TSL:5	c.1517A>T	p.Asn506Ile	missense	Exon 17 of 20	ENSP00000457308.2	H3BTS6
	TMEM87A	ENST00000704760.1		c.1514A>T	p.Asn505Ile	missense	Exon 17 of 20	ENSP00000516026.1	A0A994J4W5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1448428 Hom.: 0 Cov.: 29 AF XY: 0.00000278 AC XY: 2 AN XY: 720090

African (AFR) AF: 0.00 AC: 0 AN: 33020

American (AMR) AF: 0.00 AC: 0 AN: 42958

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25866

East Asian (EAS) AF: 0.00 AC: 0 AN: 39218

South Asian (SAS) AF: 0.00 AC: 0 AN: 83768

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53086

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5732

European-Non Finnish (NFE) AF: 0.00000181 AC: 2 AN: 1104920

Other (OTH) AF: 0.00 AC: 0 AN: 59860

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.080
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.31	T
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-0.62	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		5.5
PrimateAI	Uncertain	0.55	T
PROVEAN	Pathogenic	-6.9	D
REVEL	Benign	0.20
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.0080	D
Polyphen		0.91	P
Vest4		0.48
MutPred		0.29		Loss of solvent accessibility (P = 0.0224)
MVP		0.21
MPC		1.1
ClinPred		0.98	D
GERP RS		5.9
Varity_R		0.72
gMVP		0.46
Mutation Taster		=51/49	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs375405837; hg19: chr15-42511804;