12-106318355-G-T

Variant names:

• chr12-106318355-G-T
• rs757196033
• NM_152772.3:c.305G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_152772.3(TCP11L2):​c.305G>T​(p.Arg102Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,460,834 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign 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. R102Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: TCP11L2 NM_152772.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.476
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24541995).

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.305G>T	p.Arg102Leu	missense	Exon 4 of 10	NP_689985.1	Q8N4U5-1
	TCP11L2	NM_001286262.2		c.305G>T	p.Arg102Leu	missense	Exon 4 of 7	NP_001273191.1	Q8N4U5-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCP11L2	ENST00000299045.8	TSL:1 MANE Select	c.305G>T	p.Arg102Leu	missense	Exon 4 of 10	ENSP00000299045.3	Q8N4U5-1
	TCP11L2	ENST00000546625.5	TSL:1	c.305G>T	p.Arg102Leu	missense	Exon 4 of 6	ENSP00000449123.1	G3V1Z2
	TCP11L2	ENST00000718461.1		c.305G>T	p.Arg102Leu	missense	Exon 4 of 10	ENSP00000520839.1	Q8N4U5-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1460834 Hom.: 0 Cov.: 30 AF XY: 0.00000413 AC XY: 3 AN XY: 726788

African (AFR) AF: 0.00 AC: 0 AN: 33460

American (AMR) AF: 0.00 AC: 0 AN: 44686

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26086

East Asian (EAS) AF: 0.00 AC: 0 AN: 39660

South Asian (SAS) AF: 0.0000464 AC: 4 AN: 86152

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53362

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111356

Other (OTH) AF: 0.00 AC: 0 AN: 60310

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	14
DANN	Uncertain	1.0
DEOGEN2	Benign	0.032	T
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.43
FATHMM_MKL	Benign	0.46	N
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		0.48
PrimateAI	Benign	0.23	T
PROVEAN	Pathogenic	-4.8	D
REVEL	Benign	0.10
Sift	Uncertain	0.0050	D
Sift4G	Benign	0.27	T
Polyphen		0.81	P
Vest4		0.59
MutPred		0.70		Gain of ubiquitination at K97 (P = 0.0528)
MVP		0.40
MPC		0.11
ClinPred		0.73	D
GERP RS		2.7
Varity_R		0.21
gMVP		0.45
Mutation Taster		=86/14	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs757196033; hg19: chr12-106712133;