17-58325640-C-G

Variant names:

• chr17-58325640-C-G
• rs150017839
• NM_004758.4:c.644G>C

Variant summary

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

The NM_004758.4(TSPOAP1):​c.644G>C​(p.Arg215Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,164 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. R215L) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TSPOAP1 NM_004758.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.01
• Publications: 2 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=0.40025902).

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.644G>C	p.Arg215Pro	missense	Exon 4 of 32	NP_004749.2	O95153-1
	TSPOAP1	NM_001261835.2		c.644G>C	p.Arg215Pro	missense	Exon 4 of 32	NP_001248764.1
	TSPOAP1	NM_024418.3		c.571-638G>C		intron	N/A	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.644G>C	p.Arg215Pro	missense	Exon 4 of 32	ENSP00000345824.4	O95153-1
	TSPOAP1	ENST00000268893.10	TSL:1	c.571-638G>C		intron	N/A	ENSP00000268893.6	O95153-2
	TSPOAP1-AS1	ENST00000579527.5	TSL:2	n.191C>G		non_coding_transcript_exon	Exon 1 of 5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000400 AC: 1 AN: 249904 AF XY: 0.00

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: 0.00000887

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461164 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 726932

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52840

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5708

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111978

Other (OTH) AF: 0.00 AC: 0 AN: 60366

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.76
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.075	T
Eigen	Uncertain	0.21
Eigen_PC	Benign	0.16
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.036	D
MetaRNN	Benign	0.40	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		2.0
PrimateAI	Benign	0.39	T
PROVEAN	Uncertain	-2.5	D
REVEL	Benign	0.15
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0040	D
Polyphen		0.96	D
Vest4		0.50
MutPred		0.26		Loss of MoRF binding (P = 5e-04)
MVP		0.49
MPC		0.88
ClinPred		0.91	D
GERP RS		1.9
Varity_R		0.56
gMVP		0.40

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: rs150017839; hg19: chr17-56403001;