17-58309372-G-A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_004758.4(TSPOAP1):c.3900C>T(p.Pro1300=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000684 in 1,608,198 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 Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00014 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000060 (0 hom.)
• Consequence: TSPOAP1 NM_004758.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.16

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 Likely_benign. Variant got -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 17-58309372-G-A is Benign according to our data. Variant chr17-58309372-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 760902.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-2.16 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TSPOAP1	NM_004758.4	c.3900C>T	p.Pro1300=	synonymous_variant	22/32	ENST00000343736.9
TSPOAP1	NM_001261835.2	c.3900C>T	p.Pro1300=	synonymous_variant	22/32
TSPOAP1	NM_024418.3	c.3720C>T	p.Pro1240=	synonymous_variant	21/31

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TSPOAP1	ENST00000343736.9	c.3900C>T	p.Pro1300=	synonymous_variant	22/32	1	NM_004758.4	P2
TSPOAP1	ENST00000268893.10	c.3720C>T	p.Pro1240=	synonymous_variant	21/31	1		A2
TSPOAP1	ENST00000580669.6	c.1296C>T	p.Pro432=	synonymous_variant	6/16	5
TSPOAP1	ENST00000582679.1	c.421+595C>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.000145 AC: 22 AN: 152104 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000507

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

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

GnomAD3 exomes AF: 0.0000662 AC: 16 AN: 241652 Hom.: 0 AF XY: 0.0000609 AC XY: 8 AN XY: 131440

Gnomad AFR exome AF: 0.000761

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000546

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000280

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000604 AC: 88 AN: 1455976 Hom.: 0 Cov.: 33 AF XY: 0.0000553 AC XY: 40 AN XY: 723882

Gnomad4 AFR exome AF: 0.000449

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: 0.0000622

Gnomad4 OTH exome AF: 0.0000498

GnomAD4 genome AF: 0.000145 AC: 22 AN: 152222 Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9 AN XY: 74460

Gnomad4 AFR AF: 0.000506

Gnomad4 AMR AF: 0.0000653

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000918 Hom.: 0

Bravo AF: 0.000144

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jul 19, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
Cadd	Benign	0.28
Dann	Benign	0.51

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs191314598; hg19: chr17-56386733; COSMIC: COSV52120005; COSMIC: COSV52120005;