1-235433008-C-G

Variant names:

• chr1-235433008-C-G
• rs16832613
• NM_003193.5:c.661-1196C>G

Variant summary

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

The NM_001287801.2(TBCE):​c.723C>G​(p.Phe241Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. F241F) has been classified as Benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: TBCE NM_001287801.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0190
• Publications: 0 publications found

Genes affected

TBCE (HGNC:11582): (tubulin folding cofactor E) Cofactor E is one of four proteins (cofactors A, D, E, and C) involved in the pathway leading to correctly folded beta-tubulin from folding intermediates. Cofactors A and D are believed to play a role in capturing and stabilizing beta-tubulin intermediates in a quasi-native confirmation. Cofactor E binds to the cofactor D/beta-tubulin complex; interaction with cofactor C then causes the release of beta-tubulin polypeptides that are committed to the native state. Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2008]

ENSG00000285053 (HGNC:):

RPS21P1 (HGNC:36401): (ribosomal protein S21 pseudogene 1)

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=0.15373978).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001287801.2. 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
	TBCE	NM_003193.5	MANE Select	c.661-1196C>G		intron	N/A	NP_003184.1	Q15813-1
	TBCE	NM_001287801.2		c.723C>G	p.Phe241Leu	missense	Exon 8 of 18	NP_001274730.1	Q15813-2
	TBCE	NM_001079515.3		c.661-1196C>G		intron	N/A	NP_001072983.1	Q15813-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBCE	ENST00000642610.2	MANE Select	c.661-1196C>G		intron	N/A	ENSP00000494796.1	Q15813-1
	ENSG00000285053	ENST00000647186.1		c.661-1196C>G		intron	N/A	ENSP00000494775.1
	TBCE	ENST00000366601.8	TSL:1	c.472-1196C>G		intron	N/A	ENSP00000355560.4	A0A2U3TZJ6

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.69
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	1.0
DANN	Benign	0.60
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.0019	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.019
PROVEAN	Benign	-0.34	N
REVEL	Benign	0.048
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.98	T
Vest4		0.098
MutPred		0.56		Loss of methylation at K240 (P = 0.0295)
MVP		0.072
ClinPred		0.43	T
GERP RS		0.30
gMVP		0.18
Mutation Taster		=100/0	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: rs16832613; hg19: chr1-235596323;