rs61741210

Variant names:

• chr17-58309371-C-A
• rs61741210
• NM_004758.4:c.3901G>T

Your query was ambiguous. Multiple possible variants found:

• chr17-58309371-C-A
• chr17-58309371-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_004758.4(TSPOAP1):​c.3901G>T​(p.Asp1301Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D1301N) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TSPOAP1 NM_004758.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.46
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• TH-deficient dopa-responsive dystonia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.33853346).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004758.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSPOAP1	NM_004758.4	MANE Select	c.3901G>T	p.Asp1301Tyr	missense	Exon 22 of 32	NP_004749.2
	TSPOAP1	NM_001261835.2		c.3901G>T	p.Asp1301Tyr	missense	Exon 22 of 32	NP_001248764.1
	TSPOAP1	NM_024418.3		c.3721G>T	p.Asp1241Tyr	missense	Exon 21 of 31	NP_077729.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSPOAP1	ENST00000343736.9	TSL:1 MANE Select	c.3901G>T	p.Asp1301Tyr	missense	Exon 22 of 32	ENSP00000345824.4
	TSPOAP1	ENST00000268893.10	TSL:1	c.3721G>T	p.Asp1241Tyr	missense	Exon 21 of 31	ENSP00000268893.6
	TSPOAP1	ENST00000580669.6	TSL:5	c.1297G>T	p.Asp433Tyr	missense	Exon 6 of 16	ENSP00000462822.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Uncertain	0.084	D
BayesDel_noAF	Benign	-0.12
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.020	T
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.89	D
M_CAP	Uncertain	0.17	D
MetaRNN	Benign	0.34	T
MetaSVM	Uncertain	0.29	D
MutationAssessor	Uncertain	2.5	M
PhyloP100		1.5
PrimateAI	Benign	0.39	T
PROVEAN	Uncertain	-2.5	N
REVEL	Uncertain	0.33
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0040	D
Polyphen		0.98	D
Vest4		0.49
MutPred		0.25		Gain of catalytic residue at D1301 (P = 0.0688)
MVP		0.81
MPC		0.54
ClinPred		0.96	D
GERP RS		5.6
Varity_R		0.22
gMVP		0.35

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs61741210; hg19: chr17-56386732;