chr12-6867690-T-G

Variant names:

• chr12-6867690-T-G
• NM_000365.6:c.115+9T>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_000365.6(TPI1):​c.115+9T>G variant causes a intron 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. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 34)
• Consequence: TPI1 NM_000365.6 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.776
• Publications: 0 publications found

Genes affected

TPI1 (HGNC:12009): (triosephosphate isomerase 1) This gene encodes an enzyme, consisting of two identical proteins, which catalyzes the isomerization of glyceraldehydes 3-phosphate (G3P) and dihydroxy-acetone phosphate (DHAP) in glycolysis and gluconeogenesis. Mutations in this gene are associated with triosephosphate isomerase deficiency. Pseudogenes have been identified on chromosomes 1, 4, 6 and 7. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2009]

TPI1 Gene-Disease associations (from GenCC):

• triosephosphate isomerase deficiency

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: PanelApp Australia, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP6: Variant 12-6867690-T-G is Benign according to our data. Variant chr12-6867690-T-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3642997.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000365.6. 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
	TPI1	NM_000365.6	MANE Select	c.115+9T>G		intron	N/A	NP_000356.1	P60174-1
	TPI1	NM_001159287.1		c.226+9T>G		intron	N/A	NP_001152759.1	P60174-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TPI1	ENST00000396705.10	TSL:1 MANE Select	c.115+9T>G		intron	N/A	ENSP00000379933.4	P60174-1
	TPI1	ENST00000229270.8	TSL:1	c.226+9T>G		intron	N/A	ENSP00000229270.4	P60174-3
	TPI1	ENST00000613953.4	TSL:1	c.226+9T>G		intron	N/A	ENSP00000484435.1	P60174-3

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 34

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	2.7
DANN	Benign	0.57
PhyloP100		0.78
PromoterAI		-0.032	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

hg19: chr12-6976854;