17-58311725-G-A

Position:

• chr17-58311725-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_004758.4(TSPOAP1):​c.2930-3C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00155 in 1,556,318 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0070 (9 hom., cov: 33)
  • Exomes 𝑓: 0.00096 (11 hom.)
• Consequence: TSPOAP1 NM_004758.4 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.0002995
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.10

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP6: Variant 17-58311725-G-A is Benign according to our data. Variant chr17-58311725-G-A is described in ClinVar as [Benign]. Clinvar id is 777206.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00703 (1071/152346) while in subpopulation AFR AF= 0.0236 (980/41582). AF 95% confidence interval is 0.0223. There are 9 homozygotes in gnomad4. There are 509 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSPOAP1	NM_004758.4	c.2930-3C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000343736.9	NP_004749.2
TSPOAP1	NM_001261835.2	c.2930-3C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant			NP_001248764.1
TSPOAP1	NM_024418.3	c.2750-3C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant			NP_077729.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TSPOAP1	ENST00000343736.9	c.2930-3C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_004758.4	ENSP00000345824	P2
TSPOAP1	ENST00000268893.10	c.2750-3C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1		ENSP00000268893	A2
TSPOAP1	ENST00000580669.6	c.326-3C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		5		ENSP00000462822
TSPOAP1	ENST00000585149.1	n.98-3C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.00703 AC: 1070 AN: 152228 Hom.: 9 Cov.: 33

Gnomad AFR AF: 0.0236

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00255

Gnomad ASJ AF: 0.00231

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.000323

Gnomad OTH AF: 0.00670

GnomAD3 exomes AF: 0.00256 AC: 527 AN: 206186 Hom.: 2 AF XY: 0.00197 AC XY: 217 AN XY: 110368

Gnomad AFR exome AF: 0.0273

Gnomad AMR exome AF: 0.00125

Gnomad ASJ exome AF: 0.00214

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000138

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000458

Gnomad OTH exome AF: 0.00201

GnomAD4 exome AF: 0.000959 AC: 1346 AN: 1403972 Hom.: 11 Cov.: 33 AF XY: 0.000842 AC XY: 582 AN XY: 691430

Gnomad4 AFR exome AF: 0.0273

Gnomad4 AMR exome AF: 0.00156

Gnomad4 ASJ exome AF: 0.00208

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000115

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000180

Gnomad4 OTH exome AF: 0.00234

GnomAD4 genome AF: 0.00703 AC: 1071 AN: 152346 Hom.: 9 Cov.: 33 AF XY: 0.00683 AC XY: 509 AN XY: 74494

Gnomad4 AFR AF: 0.0236

Gnomad4 AMR AF: 0.00255

Gnomad4 ASJ AF: 0.00231

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0000941

Gnomad4 NFE AF: 0.000323

Gnomad4 OTH AF: 0.00663

Alfa AF: 0.00567 Hom.: 2

Bravo AF: 0.00801

Asia WGS AF: 0.00202 AC: 7 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	7.3
DANN	Benign	0.64

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00030
dbscSNV1_RF	Benign	0.10
SpliceAI score (max)		0.0		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: rs114867184; hg19: chr17-56389086;