rs9367980

Variant names:

• chr6-18131233-C-A
• rs9367980
• NM_000367.5:c.626-453G>T

Your query was ambiguous. Multiple possible variants found:

• chr6-18131233-C-A
• chr6-18131233-C-G
• chr6-18131233-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000367.5(TPMT):​c.626-453G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.608 in 152,054 control chromosomes in the GnomAD database, including 29,845 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.61 (29845 hom., cov: 33)
• Consequence: TPMT NM_000367.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.183
• Publications: 7 publications found

Genes affected

TPMT (HGNC:12014): (thiopurine S-methyltransferase) This gene encodes the enzyme that metabolizes thiopurine drugs via S-adenosyl-L-methionine as the S-methyl donor and S-adenosyl-L-homocysteine as a byproduct. Thiopurine drugs such as 6-mercaptopurine are used as chemotherapeutic agents. Genetic polymorphisms that affect this enzymatic activity are correlated with variations in sensitivity and toxicity to such drugs within individuals, causing thiopurine S-methyltransferase deficiency. Related pseudogenes have been identified on chromosomes 3, 18 and X. [provided by RefSeq, Aug 2014]

ENSG00000307971 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.724 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000367.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TPMT	NM_000367.5	MANE Select	c.626-453G>T		intron	N/A	NP_000358.1	P51580
	TPMT	NM_001346817.1		c.626-453G>T		intron	N/A	NP_001333746.1	P51580
	TPMT	NM_001346818.1		c.581-453G>T		intron	N/A	NP_001333747.1	P51580

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TPMT	ENST00000309983.5	TSL:1 MANE Select	c.626-453G>T		intron	N/A	ENSP00000312304.4	P51580
	TPMT	ENST00000864360.1		c.626-453G>T		intron	N/A	ENSP00000534419.1
	TPMT	ENST00000864362.1		c.626-453G>T		intron	N/A	ENSP00000534421.1

Frequencies

GnomAD3 genomes AF: 0.608 AC: 92443 AN: 151936 Hom.: 29851 Cov.: 33

Gnomad AFR AF: 0.368

Gnomad AMI AF: 0.804

Gnomad AMR AF: 0.628

Gnomad ASJ AF: 0.690

Gnomad EAS AF: 0.744

Gnomad SAS AF: 0.605

Gnomad FIN AF: 0.688

Gnomad MID AF: 0.636

Gnomad NFE AF: 0.720

Gnomad OTH AF: 0.624

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.608 AC: 92451 AN: 152054 Hom.: 29845 Cov.: 33 AF XY: 0.606 AC XY: 45059 AN XY: 74308

African (AFR) AF: 0.367 AC: 15231 AN: 41450

American (AMR) AF: 0.628 AC: 9604 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.690 AC: 2395 AN: 3472

East Asian (EAS) AF: 0.743 AC: 3845 AN: 5172

South Asian (SAS) AF: 0.606 AC: 2920 AN: 4822

European-Finnish (FIN) AF: 0.688 AC: 7259 AN: 10556

Middle Eastern (MID) AF: 0.636 AC: 187 AN: 294

European-Non Finnish (NFE) AF: 0.720 AC: 48959 AN: 67970

Other (OTH) AF: 0.623 AC: 1318 AN: 2114

Alfa AF: 0.681 Hom.: 92703

Bravo AF: 0.597

Asia WGS AF: 0.645 AC: 2240 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	6.3
DANN	Benign	0.71
PhyloP100		-0.18
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9367980; hg19: chr6-18131464;