NM_001363644.2:c.379G>A

Variant names:

• chr11-121053656-G-A
• rs527694694
• NM_001363644.2:c.379G>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001363644.2(TBCEL):​c.379G>A​(p.Gly127Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000112 in 1,612,300 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000010 (0 hom.)
• Consequence: TBCEL NM_001363644.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.82
• Publications: 0 publications found

Genes affected

TBCEL (HGNC:28115): (tubulin folding cofactor E like) Predicted to enable alpha-tubulin binding activity. Predicted to be involved in microtubule cytoskeleton organization; post-chaperonin tubulin folding pathway; and tubulin complex assembly. Predicted to be located in cytoskeleton. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

TBCEL-TECTA (HGNC:54857): (TBCEL-TECTA readthrough) Predicted to enable alpha-tubulin binding activity. Predicted to be involved in microtubule cytoskeleton organization; post-chaperonin tubulin folding pathway; and tubulin complex assembly. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.07443687).
• BS2: High AC in GnomAdExome4 at 15 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001363644.2. 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
	TBCEL	NM_001363644.2	MANE Select	c.379G>A	p.Gly127Arg	missense	Exon 5 of 9	NP_001350573.1	Q5QJ74
	TBCEL-TECTA	NM_001378761.1		c.379G>A	p.Gly127Arg	missense	Exon 4 of 30	NP_001365690.1
	TBCEL	NM_001130047.3		c.379G>A	p.Gly127Arg	missense	Exon 4 of 8	NP_001123519.1	Q5QJ74

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBCEL	ENST00000683345.1	MANE Select	c.379G>A	p.Gly127Arg	missense	Exon 5 of 9	ENSP00000507873.1	Q5QJ74
	TBCEL-TECTA	ENST00000645041.1		c.331G>A	p.Gly111Arg	missense	Exon 3 of 10	ENSP00000496315.1	A0A2R8YFB7
	TBCEL	ENST00000422003.6	TSL:1	c.379G>A	p.Gly127Arg	missense	Exon 4 of 8	ENSP00000403925.2	Q5QJ74

Frequencies

GnomAD3 genomes AF: 0.0000198 AC: 3 AN: 151698 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000295

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000239 AC: 6 AN: 250758 AF XY: 0.0000369

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000441

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000103 AC: 15 AN: 1460484 Hom.: 0 Cov.: 31 AF XY: 0.0000110 AC XY: 8 AN XY: 726562

African (AFR) AF: 0.00 AC: 0 AN: 33388

American (AMR) AF: 0.00 AC: 0 AN: 44554

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26064

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.00 AC: 0 AN: 86230

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53372

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5754

European-Non Finnish (NFE) AF: 0.0000126 AC: 14 AN: 1111134

Other (OTH) AF: 0.0000166 AC: 1 AN: 60302

GnomAD4 genome AF: 0.0000198 AC: 3 AN: 151816 Hom.: 0 Cov.: 32 AF XY: 0.0000270 AC XY: 2 AN XY: 74198

African (AFR) AF: 0.00 AC: 0 AN: 41466

American (AMR) AF: 0.00 AC: 0 AN: 15204

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3462

East Asian (EAS) AF: 0.000195 AC: 1 AN: 5138

South Asian (SAS) AF: 0.00 AC: 0 AN: 4802

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000295 AC: 2 AN: 67834

Other (OTH) AF: 0.00 AC: 0 AN: 2106

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000189

ExAC AF: 0.0000330 AC: 4

EpiCase AF: 0.000109

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	21
DANN	Benign	0.90
DEOGEN2	Benign	0.017	T
Eigen	Benign	-0.078
Eigen_PC	Benign	0.17
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.0041	T
MetaRNN	Benign	0.074	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.59	N
PhyloP100		3.8
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	0.84	N
REVEL	Benign	0.073
Sift	Benign	0.58	T
Sift4G	Benign	0.31	T
Polyphen		0.0010	B
Vest4		0.23
MutPred		0.42		Gain of MoRF binding (P = 0.0085)
MVP		0.093
MPC		0.90
ClinPred		0.15	T
GERP RS		6.0
Varity_R		0.078
gMVP		0.61
Mutation Taster		=56/44	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: rs527694694; hg19: chr11-120924365;