rs763316290

Variant names:

• chr17-58308839-C-A
• NM_004758.4:c.4433G>T

Your query was ambiguous. Multiple possible variants found:

• chr17-58308839-C-A
• chr17-58308839-C-G
• chr17-58308839-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004758.4(TSPOAP1):​c.4433G>T​(p.Arg1478Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,458,984 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: TSPOAP1 NM_004758.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0230

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16886103).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSPOAP1	NM_004758.4	c.4433G>T	p.Arg1478Leu	missense_variant	Exon 22 of 32	ENST00000343736.9	NP_004749.2
TSPOAP1	NM_001261835.2	c.4433G>T	p.Arg1478Leu	missense_variant	Exon 22 of 32		NP_001248764.1
TSPOAP1	NM_024418.3	c.4253G>T	p.Arg1418Leu	missense_variant	Exon 21 of 31		NP_077729.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TSPOAP1	ENST00000343736.9	c.4433G>T	p.Arg1478Leu	missense_variant	Exon 22 of 32	1	NM_004758.4	ENSP00000345824.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1458984 Hom.: 0 Cov.: 42 AF XY: 0.00000138 AC XY: 1 AN XY: 725644

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	16
DANN	Uncertain	1.0
DEOGEN2	Benign	0.021	.;.;T
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.23
FATHMM_MKL	Benign	0.13	N
LIST_S2	Uncertain	0.91	D;D;D
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.17	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	.;.;M
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-1.6	N;.;N
REVEL	Benign	0.075
Sift	Uncertain	0.0070	D;.;D
Sift4G	Benign	0.68	T;.;T
Polyphen		0.90	P;.;P
Vest4		0.43
MutPred		0.28		.;.;Loss of methylation at R1478 (P = 0.0126);
MVP		0.19
MPC		0.80
ClinPred		0.77	D
GERP RS		4.2
Varity_R		0.16
gMVP		0.64

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-56386200;