rs1489012728

Variant names:

• chr17-58324995-G-A
• rs1489012728
• NM_004758.4:c.758C>T

Your query was ambiguous. Multiple possible variants found:

• chr17-58324995-G-A
• chr17-58324995-G-T

Variant summary

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

The NM_004758.4(TSPOAP1):​c.758C>T​(p.Pro253Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000326 in 1,532,670 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000022 (0 hom.)
• Consequence: TSPOAP1 NM_004758.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.88
• Publications: 0 publications found

Genes affected

TSPOAP1 (HGNC:16831): (TSPO associated protein 1) Enables benzodiazepine receptor binding activity. Predicted to be involved in regulation of presynaptic cytosolic calcium ion concentration. Located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

TSPOAP1-AS1 (HGNC:44148): (TSPOAP1, SUPT4H1 and RNF43 antisense RNA 1)

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=0.32651287).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004758.4. 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
	TSPOAP1	NM_004758.4	MANE Select	c.758C>T	p.Pro253Leu	missense	Exon 5 of 32	NP_004749.2	O95153-1
	TSPOAP1	NM_001261835.2		c.758C>T	p.Pro253Leu	missense	Exon 5 of 32	NP_001248764.1
	TSPOAP1	NM_024418.3		c.578C>T	p.Pro193Leu	missense	Exon 4 of 31	NP_077729.1	O95153-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSPOAP1	ENST00000343736.9	TSL:1 MANE Select	c.758C>T	p.Pro253Leu	missense	Exon 5 of 32	ENSP00000345824.4	O95153-1
	TSPOAP1	ENST00000268893.10	TSL:1	c.578C>T	p.Pro193Leu	missense	Exon 4 of 31	ENSP00000268893.6	O95153-2
	TSPOAP1-AS1	ENST00000667382.1		n.156+368G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152094 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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

GnomAD2 exomes AF: 0.00000762 AC: 1 AN: 131192 AF XY: 0.0000142

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS 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: 0.00000217 AC: 3 AN: 1380576 Hom.: 0 Cov.: 32 AF XY: 0.00000294 AC XY: 2 AN XY: 679812

African (AFR) AF: 0.00 AC: 0 AN: 31296

American (AMR) AF: 0.00 AC: 0 AN: 34950

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24502

East Asian (EAS) AF: 0.00 AC: 0 AN: 35564

South Asian (SAS) AF: 0.0000129 AC: 1 AN: 77598

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43040

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4034

European-Non Finnish (NFE) AF: 0.00000187 AC: 2 AN: 1072360

Other (OTH) AF: 0.00 AC: 0 AN: 57232

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152094 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74290

African (AFR) AF: 0.0000483 AC: 2 AN: 41424

American (AMR) AF: 0.00 AC: 0 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67978

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

ClinVar

ClinVar submissions as Germline

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	Benign	0.19
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.078	T
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.33	T
MetaSVM	Benign	-1.2	T
MutationAssessor	Benign	1.9	L
PhyloP100		2.9
PrimateAI	Uncertain	0.60	T
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.14
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0030	D
Polyphen		1.0	D
Vest4		0.34
MutPred		0.32		Gain of catalytic residue at P253 (P = 0.0015)
MVP		0.44
MPC		0.44
ClinPred		0.99	D
GERP RS		5.0
Varity_R		0.26
gMVP		0.41
Mutation Taster		=90/10	polymorphism

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: rs1489012728; hg19: chr17-56402356;