chr12-106335654-C-T

Variant names:

• chr12-106335654-C-T
• rs185429315
• NM_152772.3:c.788C>T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_152772.3(TCP11L2):​c.788C>T​(p.Thr263Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,836 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. T263S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TCP11L2 NM_152772.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.43
• Publications: 0 publications found

Genes affected

TCP11L2 (HGNC:28627): (t-complex 11 like 2) Predicted to be involved in signal transduction. [provided by Alliance of Genome Resources, Apr 2022]

TCP11L2 Gene-Disease associations (from GenCC):

• schizophrenia

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.927

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152772.3. 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
	TCP11L2	NM_152772.3	MANE Select	c.788C>T	p.Thr263Ile	missense	Exon 7 of 10	NP_689985.1	Q8N4U5-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCP11L2	ENST00000299045.8	TSL:1 MANE Select	c.788C>T	p.Thr263Ile	missense	Exon 7 of 10	ENSP00000299045.3	Q8N4U5-1
	TCP11L2	ENST00000718461.1		c.788C>T	p.Thr263Ile	missense	Exon 7 of 10	ENSP00000520839.1	Q8N4U5-1
	TCP11L2	ENST00000910255.1		c.788C>T	p.Thr263Ile	missense	Exon 8 of 11	ENSP00000580314.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461836 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727212

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111986

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.92
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.080
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.21	T
Eigen	Pathogenic	0.89
Eigen_PC	Pathogenic	0.86
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.054	D
MetaRNN	Pathogenic	0.93	D
MetaSVM	Benign	-0.76	T
MutationAssessor	Pathogenic	3.4	M
PhyloP100		5.4
PrimateAI	Uncertain	0.64	T
PROVEAN	Uncertain	-3.9	D
REVEL	Uncertain	0.40
Sift	Uncertain	0.028	D
Sift4G	Uncertain	0.0080	D
Polyphen		0.97	D
Vest4		0.94
MutPred		0.74		Loss of disorder (P = 0.0404)
MVP		0.49
MPC		0.34
ClinPred		1.0	D
GERP RS		6.0
Varity_R		0.52
gMVP		0.86
Mutation Taster		=43/57	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: rs185429315; hg19: chr12-106729432;