rs61743284

Positions:

• chr17-58327685-C-T

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.236G>A​(p.Gly79Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0226 in 1,613,940 control chromosomes in the GnomAD database, including 508 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.018 (32 hom., cov: 32)
  • Exomes 𝑓: 0.023 (476 hom.)
• Consequence: TSPOAP1 NM_004758.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.232

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

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0019398034).
• BP6: Variant 17-58327685-C-T is Benign according to our data. Variant chr17-58327685-C-T is described in ClinVar as [Benign]. Clinvar id is 402438.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.018 (2745/152348) while in subpopulation SAS AF= 0.0281 (136/4834). AF 95% confidence interval is 0.0243. There are 32 homozygotes in gnomad4. There are 1365 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 32 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TSPOAP1	NM_004758.4	c.236G>A	p.Gly79Glu	missense_variant	1/32	ENST00000343736.9
TSPOAP1-AS1	NR_038410.1	n.280-365C>T		intron_variant, non_coding_transcript_variant
TSPOAP1	NM_001261835.2	c.236G>A	p.Gly79Glu	missense_variant	1/32
TSPOAP1	NM_024418.3	c.236G>A	p.Gly79Glu	missense_variant	1/31

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TSPOAP1	ENST00000343736.9	c.236G>A	p.Gly79Glu	missense_variant	1/32	1	NM_004758.4	P2

Frequencies

GnomAD3 genomes AF: 0.0181 AC: 2748 AN: 152230 Hom.: 32 Cov.: 32

Gnomad AFR AF: 0.00540

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.0171

Gnomad ASJ AF: 0.0510

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0285

Gnomad FIN AF: 0.0240

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0238

Gnomad OTH AF: 0.0239

GnomAD3 exomes AF: 0.0217 AC: 5452 AN: 251178 Hom.: 96 AF XY: 0.0232 AC XY: 3149 AN XY: 135892

Gnomad AFR exome AF: 0.00536

Gnomad AMR exome AF: 0.0119

Gnomad ASJ exome AF: 0.0469

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.0331

Gnomad FIN exome AF: 0.0244

Gnomad NFE exome AF: 0.0244

Gnomad OTH exome AF: 0.0276

GnomAD4 exome AF: 0.0231 AC: 33735 AN: 1461592 Hom.: 476 Cov.: 31 AF XY: 0.0240 AC XY: 17452 AN XY: 727110

Gnomad4 AFR exome AF: 0.00550

Gnomad4 AMR exome AF: 0.0122

Gnomad4 ASJ exome AF: 0.0468

Gnomad4 EAS exome AF: 0.000126

Gnomad4 SAS exome AF: 0.0323

Gnomad4 FIN exome AF: 0.0233

Gnomad4 NFE exome AF: 0.0235

Gnomad4 OTH exome AF: 0.0239

GnomAD4 genome AF: 0.0180 AC: 2745 AN: 152348 Hom.: 32 Cov.: 32 AF XY: 0.0183 AC XY: 1365 AN XY: 74500

Gnomad4 AFR AF: 0.00539

Gnomad4 AMR AF: 0.0171

Gnomad4 ASJ AF: 0.0510

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0281

Gnomad4 FIN AF: 0.0240

Gnomad4 NFE AF: 0.0237

Gnomad4 OTH AF: 0.0237

Alfa AF: 0.0238 Hom.: 26

Bravo AF: 0.0170

TwinsUK AF: 0.0218 AC: 81

ALSPAC AF: 0.0210 AC: 81

ESP6500AA AF: 0.00749 AC: 33

ESP6500EA AF: 0.0260 AC: 224

ExAC AF: 0.0217 AC: 2633

Asia WGS AF: 0.0120 AC: 43 AN: 3478

EpiCase AF: 0.0267

EpiControl AF: 0.0279

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.67	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	12
DANN	Benign	0.69
DEOGEN2	Benign	0.0089	.;T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.64	D
LIST_S2	Benign	0.64	T;T
MetaRNN	Benign	0.0019	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.97	L;L
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.75	N;N
REVEL	Benign	0.078
Sift	Benign	0.066	T;T
Sift4G	Benign	0.33	T;T
Polyphen		0.68	P;B
Vest4		0.065
MPC		0.27
ClinPred		0.0023	T
GERP RS		0.89
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.064
gMVP		0.085

Splicing

Name	Calibrated prediction	Score	Prediction
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: rs61743284; hg19: chr17-56405046; COSMIC: COSV52108730; COSMIC: COSV52108730;