17-58305843-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_004758.4(TSPOAP1):c.5247G>A(p.Gln1749=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000434 in 1,612,946 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00027 (2 hom., cov: 32)
  • Exomes 𝑓: 0.00045 (6 hom.)
• Consequence: TSPOAP1 NM_004758.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.268

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 Benign. Variant got -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP6: Variant 17-58305843-C-T is Benign according to our data. Variant chr17-58305843-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2647958.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.268 with no splicing effect.
• BS2: High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TSPOAP1	NM_004758.4	c.5247G>A	p.Gln1749=	synonymous_variant	27/32	ENST00000343736.9
TSPOAP1	NM_001261835.2	c.5220G>A	p.Gln1740=	synonymous_variant	27/32
TSPOAP1	NM_024418.3	c.5067G>A	p.Gln1689=	synonymous_variant	26/31

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TSPOAP1	ENST00000343736.9	c.5247G>A	p.Gln1749=	synonymous_variant	27/32	1	NM_004758.4	P2

Frequencies

GnomAD3 genomes AF: 0.000263 AC: 40 AN: 152172 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00662

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000870 AC: 217 AN: 249544 Hom.: 2 AF XY: 0.00115 AC XY: 155 AN XY: 135248

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000116

Gnomad ASJ exome AF: 0.000800

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00602

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000160

Gnomad OTH exome AF: 0.000493

GnomAD4 exome AF: 0.000451 AC: 659 AN: 1460656 Hom.: 6 Cov.: 33 AF XY: 0.000651 AC XY: 473 AN XY: 726702

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.000112

Gnomad4 ASJ exome AF: 0.00119

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00581

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000576

Gnomad4 OTH exome AF: 0.000630

GnomAD4 genome AF: 0.000269 AC: 41 AN: 152290 Hom.: 2 Cov.: 32 AF XY: 0.000376 AC XY: 28 AN XY: 74466

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00144

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00684

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000441

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000172 Hom.: 0

Bravo AF: 0.000110

Asia WGS AF: 0.00318 AC: 12 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.000119

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

CeGaT Center for Human Genetics Tuebingen

Sep 01, 2022

TSPOAP1: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
Cadd	Benign	4.5
Dann	Benign	0.60

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

LitVar

Other links and lift over

dbSNP: rs148464443; hg19: chr17-56383204;