11-33065899-G-A

Variant names:

• chr11-33065899-G-A
• rs137983400
• NM_018393.4:c.1042G>A

Variant summary

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

The NM_018393.4(TCP11L1):​c.1042G>A​(p.Ala348Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,854 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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. A348S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: TCP11L1 NM_018393.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.33
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22314525).

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.1042G>A	p.Ala348Thr	missense	Exon 8 of 10	NP_060863.3
	TCP11L1	NM_001145541.1		c.1042G>A	p.Ala348Thr	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.1042G>A	p.Ala348Thr	missense	Exon 8 of 10	ENSP00000335595.4	Q9NUJ3
	TCP11L1	ENST00000862423.1		c.1057G>A	p.Ala353Thr	missense	Exon 8 of 10	ENSP00000532482.1
	TCP11L1	ENST00000432887.5	TSL:5	c.1042G>A	p.Ala348Thr	missense	Exon 8 of 10	ENSP00000395070.1	Q9NUJ3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461854 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727230

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

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111980

Other (OTH) AF: 0.00 AC: 0 AN: 60392

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.011	T
Eigen	Benign	-0.10
Eigen_PC	Benign	0.072
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.0040	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
PhyloP100		4.3
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.82	N
REVEL	Benign	0.055
Sift	Benign	0.59	T
Sift4G	Benign	0.42	T
Polyphen		0.022	B
Vest4		0.41
MutPred		0.67		Loss of helix (P = 0.0167)
MVP		0.23
MPC		0.44
ClinPred		0.55	D
GERP RS		5.3
Varity_R		0.051
gMVP		0.24
Mutation Taster		=71/29	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: rs137983400; hg19: chr11-33087445; COSMIC: COSV57517955; COSMIC: COSV57517955;