11-33065897-G-C

Variant names:

• chr11-33065897-G-C
• rs1167091996
• NM_018393.4:c.1040G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_018393.4(TCP11L1):​c.1040G>C​(p.Gly347Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 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. G347E) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TCP11L1 NM_018393.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.88
• Publications: 0 publications found

Genes affected

TCP11L1 (HGNC:25655): (t-complex 11 like 1) Predicted to be involved in signal transduction. Located in microtubule. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.374744).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018393.4. 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
	TCP11L1	NM_018393.4	MANE Select	c.1040G>C	p.Gly347Ala	missense	Exon 8 of 10	NP_060863.3
	TCP11L1	NM_001145541.1		c.1040G>C	p.Gly347Ala	missense	Exon 8 of 10	NP_001139013.1	Q9NUJ3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCP11L1	ENST00000334274.9	TSL:1 MANE Select	c.1040G>C	p.Gly347Ala	missense	Exon 8 of 10	ENSP00000335595.4	Q9NUJ3
	TCP11L1	ENST00000862423.1		c.1055G>C	p.Gly352Ala	missense	Exon 8 of 10	ENSP00000532482.1
	TCP11L1	ENST00000432887.5	TSL:5	c.1040G>C	p.Gly347Ala	missense	Exon 8 of 10	ENSP00000395070.1	Q9NUJ3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	21
DANN	Benign	0.72
DEOGEN2	Benign	0.0044	T
Eigen	Benign	0.063
Eigen_PC	Benign	0.20
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.37	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.94	L
PhyloP100		6.9
PrimateAI	Benign	0.44	T
PROVEAN	Benign	0.89	N
REVEL	Benign	0.18
Sift	Benign	1.0	T
Sift4G	Benign	0.88	T
Polyphen		0.77	P
Vest4		0.39
MutPred		0.72		Gain of catalytic residue at G347 (P = 0.1353)
MVP		0.27
MPC		0.62
ClinPred		0.64	D
GERP RS		5.5
Varity_R		0.096
gMVP		0.32
Mutation Taster		=70/30	polymorphism

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: rs1167091996; hg19: chr11-33087443;