rs61741210

chr17-58309371-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_004758.4(TSPOAP1):c.3901G>A(p.Asp1301Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0231 in 1,608,002 control chromosomes in the GnomAD database, including 541 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.018 (33 hom., cov: 32)
  • Exomes 𝑓: 0.024 (508 hom.)
• Consequence: TSPOAP1 NM_004758.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.46

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.002943635).
• BP6: Variant 17-58309371-C-T is Benign according to our data. Variant chr17-58309371-C-T is described in ClinVar as [Benign]. Clinvar id is 402437.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-58309371-C-T is described in Lovd as [Benign].
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0183 (2777/152156) while in subpopulation SAS AF= 0.0305 (147/4816). AF 95% confidence interval is 0.0265. There are 33 homozygotes in gnomad4. There are 1376 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 33 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TSPOAP1	NM_004758.4	c.3901G>A	p.Asp1301Asn	missense_variant	22/32	ENST00000343736.9
TSPOAP1	NM_001261835.2	c.3901G>A	p.Asp1301Asn	missense_variant	22/32
TSPOAP1	NM_024418.3	c.3721G>A	p.Asp1241Asn	missense_variant	21/31

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TSPOAP1	ENST00000343736.9	c.3901G>A	p.Asp1301Asn	missense_variant	22/32	1	NM_004758.4	P2
TSPOAP1	ENST00000268893.10	c.3721G>A	p.Asp1241Asn	missense_variant	21/31	1		A2
TSPOAP1	ENST00000580669.6	c.1297G>A	p.Asp433Asn	missense_variant	6/16	5
TSPOAP1	ENST00000582679.1	c.421+596G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.0183 AC: 2779 AN: 152038 Hom.: 33 Cov.: 32

Gnomad AFR AF: 0.00394

Gnomad AMI AF: 0.0176

Gnomad AMR AF: 0.0181

Gnomad ASJ AF: 0.0545

Gnomad EAS AF: 0.000387

Gnomad SAS AF: 0.0307

Gnomad FIN AF: 0.0239

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0245

Gnomad OTH AF: 0.0259

GnomAD3 exomes AF: 0.0226 AC: 5462 AN: 241648 Hom.: 99 AF XY: 0.0243 AC XY: 3196 AN XY: 131454

Gnomad AFR exome AF: 0.00387

Gnomad AMR exome AF: 0.0120

Gnomad ASJ exome AF: 0.0530

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.0364

Gnomad FIN exome AF: 0.0249

Gnomad NFE exome AF: 0.0252

Gnomad OTH exome AF: 0.0275

GnomAD4 exome AF: 0.0236 AC: 34343 AN: 1455846 Hom.: 508 Cov.: 34 AF XY: 0.0246 AC XY: 17827 AN XY: 723784

Gnomad4 AFR exome AF: 0.00392

Gnomad4 AMR exome AF: 0.0126

Gnomad4 ASJ exome AF: 0.0521

Gnomad4 EAS exome AF: 0.000126

Gnomad4 SAS exome AF: 0.0355

Gnomad4 FIN exome AF: 0.0233

Gnomad4 NFE exome AF: 0.0238

Gnomad4 OTH exome AF: 0.0242

GnomAD4 genome AF: 0.0183 AC: 2777 AN: 152156 Hom.: 33 Cov.: 32 AF XY: 0.0185 AC XY: 1376 AN XY: 74386

Gnomad4 AFR AF: 0.00393

Gnomad4 AMR AF: 0.0180

Gnomad4 ASJ AF: 0.0545

Gnomad4 EAS AF: 0.000388

Gnomad4 SAS AF: 0.0305

Gnomad4 FIN AF: 0.0239

Gnomad4 NFE AF: 0.0245

Gnomad4 OTH AF: 0.0256

Alfa AF: 0.0245 Hom.: 79

Bravo AF: 0.0170

TwinsUK AF: 0.0218 AC: 81

ALSPAC AF: 0.0223 AC: 86

ESP6500AA AF: 0.00568 AC: 25

ESP6500EA AF: 0.0259 AC: 223

ExAC AF: 0.0224 AC: 2715

Asia WGS AF: 0.0120 AC: 40 AN: 3478

EpiCase AF: 0.0280

EpiControl AF: 0.0292

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

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 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.42
Cadd	Benign	21
Dann	Uncertain	1.0
Eigen	Benign	0.053
Eigen_PC	Benign	0.18
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.76	T;T;T
MetaRNN	Benign	0.0029	T;T;T
MetaSVM	Benign	-0.49	T
MutationTaster	Benign	0.98	N;N;N
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-1.5	N;.;N
REVEL	Benign	0.22
Sift	Uncertain	0.018	D;.;D
Sift4G	Uncertain	0.045	D;.;D
Polyphen		0.014	B;.;B
Vest4		0.28
MPC		0.21
ClinPred		0.011	T
GERP RS		5.6
Varity_R		0.13
gMVP		0.20

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs61741210; hg19: chr17-56386732; COSMIC: COSV52108620; COSMIC: COSV52108620;