rs2273549

chr11-33058034-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018393.4(TCP11L1):c.533A>G(p.Lys178Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 1,613,928 control chromosomes in the GnomAD database, including 22,221 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.14 (1669 hom., cov: 31)
  • Exomes 𝑓: 0.16 (20552 hom.)
• Consequence: TCP11L1 NM_018393.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.41

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0012417734).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.168 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TCP11L1	NM_018393.4	c.533A>G	p.Lys178Arg	missense_variant	5/10	ENST00000334274.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TCP11L1	ENST00000334274.9	c.533A>G	p.Lys178Arg	missense_variant	5/10	1	NM_018393.4	P1

Frequencies

GnomAD3 genomes AF: 0.143 AC: 21765 AN: 151958 Hom.: 1669 Cov.: 31

Gnomad AFR AF: 0.0928

Gnomad AMI AF: 0.178

Gnomad AMR AF: 0.142

Gnomad ASJ AF: 0.218

Gnomad EAS AF: 0.118

Gnomad SAS AF: 0.101

Gnomad FIN AF: 0.166

Gnomad MID AF: 0.220

Gnomad NFE AF: 0.170

Gnomad OTH AF: 0.164

GnomAD3 exomes AF: 0.151 AC: 37908 AN: 251366 Hom.: 3163 AF XY: 0.152 AC XY: 20663 AN XY: 135856

Gnomad AFR exome AF: 0.0936

Gnomad AMR exome AF: 0.119

Gnomad ASJ exome AF: 0.220

Gnomad EAS exome AF: 0.122

Gnomad SAS exome AF: 0.113

Gnomad FIN exome AF: 0.170

Gnomad NFE exome AF: 0.172

Gnomad OTH exome AF: 0.170

GnomAD4 exome AF: 0.164 AC: 240422 AN: 1461852 Hom.: 20552 Cov.: 34 AF XY: 0.164 AC XY: 119045 AN XY: 727226

Gnomad4 AFR exome AF: 0.0870

Gnomad4 AMR exome AF: 0.119

Gnomad4 ASJ exome AF: 0.217

Gnomad4 EAS exome AF: 0.114

Gnomad4 SAS exome AF: 0.117

Gnomad4 FIN exome AF: 0.170

Gnomad4 NFE exome AF: 0.172

Gnomad4 OTH exome AF: 0.169

GnomAD4 genome AF: 0.143 AC: 21765 AN: 152076 Hom.: 1669 Cov.: 31 AF XY: 0.141 AC XY: 10514 AN XY: 74330

Gnomad4 AFR AF: 0.0927

Gnomad4 AMR AF: 0.142

Gnomad4 ASJ AF: 0.218

Gnomad4 EAS AF: 0.118

Gnomad4 SAS AF: 0.101

Gnomad4 FIN AF: 0.166

Gnomad4 NFE AF: 0.170

Gnomad4 OTH AF: 0.162

Alfa AF: 0.171 Hom.: 6125

Bravo AF: 0.142

TwinsUK AF: 0.166 AC: 617

ALSPAC AF: 0.180 AC: 695

ESP6500AA AF: 0.100 AC: 442

ESP6500EA AF: 0.179 AC: 1535

ExAC AF: 0.149 AC: 18134

Asia WGS AF: 0.0860 AC: 301 AN: 3478

EpiCase AF: 0.184

EpiControl AF: 0.189

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.75	T
BayesDel_noAF	Benign	-0.71
Cadd	Benign	15
Dann	Benign	0.50
DEOGEN2	Benign	0.0032	T;T;T
Eigen	Benign	-0.92
Eigen_PC	Benign	-0.81
FATHMM_MKL	Benign	0.56	D
MetaRNN	Benign	0.0012	T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.97	L;L;L
MutationTaster	Benign	1.0	P;P;P
PrimateAI	Benign	0.39	T
PROVEAN	Benign	0.070	N;N;N
REVEL	Benign	0.021
Sift	Benign	0.74	T;T;T
Sift4G	Benign	0.69	T;T;T
Polyphen		0.0030	B;B;B
Vest4		0.026
MPC		0.22
ClinPred		0.0010	T
GERP RS		0.69
Varity_R		0.019
gMVP		0.17

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

Publications

LitVar

Other links and lift over

dbSNP: rs2273549; hg19: chr11-33079580; COSMIC: COSV57515619; COSMIC: COSV57515619;