22-37018519-C-T

Position:

• chr22-37018519-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_003312.6(TST):​c.214G>A​(p.Glu72Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000139 in 1,442,196 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: TST NM_003312.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.09

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.36470908).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TST	NM_003312.6	c.214G>A	p.Glu72Lys	missense_variant	2/3	ENST00000249042.8
TST	NM_001270483.1	c.214G>A	p.Glu72Lys	missense_variant	2/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TST	ENST00000249042.8	c.214G>A	p.Glu72Lys	missense_variant	2/3	1	NM_003312.6	P1
TST	ENST00000403892.7	c.214G>A	p.Glu72Lys	missense_variant	1/2	1		P1
TST	ENST00000622841.1	c.214G>A	p.Glu72Lys	missense_variant	2/3	5		P1
TST	ENST00000438203.1	c.214G>A	p.Glu72Lys	missense_variant	2/2	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000139 AC: 2 AN: 1442196 Hom.: 0 Cov.: 31 AF XY: 0.00000279 AC XY: 2 AN XY: 715664

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000258

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.07e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.41
BayesDel_addAF	Benign	-0.071	T
BayesDel_noAF	Benign	-0.34
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.087	T;T;T;.
Eigen	Benign	-0.043
Eigen_PC	Benign	0.10
FATHMM_MKL	Uncertain	0.96	D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.36	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L;L;L;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-1.7	N;N;.;N
REVEL	Benign	0.15
Sift	Benign	0.10	T;T;.;T
Sift4G	Benign	0.78	T;T;T;T
Polyphen		0.031	B;B;B;.
Vest4		0.27
MutPred		0.57		Gain of ubiquitination at E72 (P = 0.0238);Gain of ubiquitination at E72 (P = 0.0238);Gain of ubiquitination at E72 (P = 0.0238);Gain of ubiquitination at E72 (P = 0.0238);
MVP		0.28
MPC		1.2
ClinPred		0.91	D
GERP RS		4.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.23
gMVP		0.50

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-37414560;