NM_018393.4:c.533A>G

Variant names:

• chr11-33058034-A-G
• rs2273549
• NM_018393.4:c.533A>G

Variant summary

Our verdict is Benign. The variant received -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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 31 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: Benign. The variant received -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 rank	MANE	Protein	UniProt
TCP11L1	NM_018393.4	c.533A>G	p.Lys178Arg	missense_variant	Exon 5 of 10	ENST00000334274.9	NP_060863.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TCP11L1	ENST00000334274.9	c.533A>G	p.Lys178Arg	missense_variant	Exon 5 of 10	1	NM_018393.4	ENSP00000335595.4

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

GnomAD2 exomes AF: 0.151 AC: 37908 AN: 251366 AF XY: 0.152

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 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

African (AFR) AF: 0.0870 AC: 2911 AN: 33478

American (AMR) AF: 0.119 AC: 5334 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.217 AC: 5673 AN: 26136

East Asian (EAS) AF: 0.114 AC: 4521 AN: 39696

South Asian (SAS) AF: 0.117 AC: 10061 AN: 86256

European-Finnish (FIN) AF: 0.170 AC: 9100 AN: 53412

Middle Eastern (MID) AF: 0.202 AC: 1167 AN: 5768

European-Non Finnish (NFE) AF: 0.172 AC: 191447 AN: 1111990

Other (OTH) AF: 0.169 AC: 10208 AN: 60394

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

African (AFR) AF: 0.0927 AC: 3848 AN: 41498

American (AMR) AF: 0.142 AC: 2162 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.218 AC: 757 AN: 3472

East Asian (EAS) AF: 0.118 AC: 609 AN: 5182

South Asian (SAS) AF: 0.101 AC: 485 AN: 4822

European-Finnish (FIN) AF: 0.166 AC: 1749 AN: 10546

Middle Eastern (MID) AF: 0.226 AC: 66 AN: 292

European-Non Finnish (NFE) AF: 0.170 AC: 11585 AN: 67978

Other (OTH) AF: 0.162 AC: 342 AN: 2106

Alfa AF: 0.165 Hom.: 10994

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
LIST_S2	Benign	0.73	.;T;.
MetaRNN	Benign	0.0012	T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.97	L;L;L
PhyloP100		1.4
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
Mutation Taster		=100/0	polymorphism (auto)

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