22-37011067-G-T

Position:

• chr22-37011067-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_003312.6(TST):​c.854C>A​(p.Pro285Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,459,566 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: TST NM_003312.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.48

Genes affected

TST (HGNC:12388): (thiosulfate sulfurtransferase) This is one of two neighboring genes encoding similar proteins that each contain two rhodanese domains. The encoded protein is localized to the mitochondria and catalyzes the conversion of thiosulfate and cyanide to thiocyanate and sulfite. In addition, the protein interacts with 5S ribosomal RNA and facilitates its import into the mitochondria. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2012]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TST	NM_003312.6	c.854C>A	p.Pro285Gln	missense_variant	3/3	ENST00000249042.8
TST	NM_001270483.1	c.854C>A	p.Pro285Gln	missense_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TST	ENST00000249042.8	c.854C>A	p.Pro285Gln	missense_variant	3/3	1	NM_003312.6	P1
TST	ENST00000403892.7	c.854C>A	p.Pro285Gln	missense_variant	2/2	1		P1
TST	ENST00000622841.1	c.854C>A	p.Pro285Gln	missense_variant	3/3	5		P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000805 AC: 2 AN: 248532 Hom.: 0 AF XY: 0.00000741 AC XY: 1 AN XY: 134996

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000545

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1459566 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2 AN XY: 726038

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0000348

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.082	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.38	T;T;T
Eigen	Benign	0.18
Eigen_PC	Benign	0.15
FATHMM_MKL	Uncertain	0.92	D
M_CAP	Benign	0.076	D
MetaRNN	Uncertain	0.64	D;D;D
MetaSVM	Benign	-0.54	T
MutationAssessor	Pathogenic	3.2	M;M;M
MutationTaster	Benign	1.0	D;D
PrimateAI	Benign	0.35	T
PROVEAN	Uncertain	-4.1	D;D;.
REVEL	Benign	0.24
Sift	Uncertain	0.0020	D;D;.
Sift4G	Uncertain	0.027	D;D;D
Polyphen		0.80	P;P;P
Vest4		0.52
MutPred		0.35		Loss of catalytic residue at P284 (P = 0.0131);Loss of catalytic residue at P284 (P = 0.0131);Loss of catalytic residue at P284 (P = 0.0131);
MVP		0.53
MPC		0.95
ClinPred		0.98	D
GERP RS		4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.44
gMVP		0.71

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: rs900257476; hg19: chr22-37407108;