chr1-235433008-C-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001287801.2(TBCE):​c.723C>T​(p.Phe241Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00425 in 1,521,900 control chromosomes in the GnomAD database, including 233 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.022 (137 hom., cov: 31)
  • Exomes 𝑓: 0.0022 (96 hom.)
• Consequence: TBCE NM_001287801.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• 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: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 1-235433008-C-T is Benign according to our data. Variant chr1-235433008-C-T is described in ClinVar as Benign. ClinVar VariationId is 1270754.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.019 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0749 is higher than 0.05.

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>T		intron	N/A	NP_003184.1	Q15813-1
	TBCE	NM_001287801.2		c.723C>T	p.Phe241Phe	synonymous	Exon 8 of 18	NP_001274730.1	Q15813-2
	TBCE	NM_001079515.3		c.661-1196C>T		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>T		intron	N/A	ENSP00000494796.1	Q15813-1
	ENSG00000285053	ENST00000647186.1		c.661-1196C>T		intron	N/A	ENSP00000494775.1
	TBCE	ENST00000366601.8	TSL:1	c.472-1196C>T		intron	N/A	ENSP00000355560.4	A0A2U3TZJ6

Frequencies

GnomAD3 genomes AF: 0.0222 AC: 3371 AN: 151530 Hom.: 136 Cov.: 31

Gnomad AFR AF: 0.0769

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00810

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000416

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00321

Gnomad NFE AF: 0.000529

Gnomad OTH AF: 0.0187

GnomAD2 exomes AF: 0.00433 AC: 563 AN: 130050 AF XY: 0.00353

Gnomad AFR exome AF: 0.0698

Gnomad AMR exome AF: 0.00469

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000539

Gnomad OTH exome AF: 0.00287

GnomAD4 exome AF: 0.00225 AC: 3077 AN: 1370260 Hom.: 96 Cov.: 31 AF XY: 0.00195 AC XY: 1316 AN XY: 676288

African (AFR) AF: 0.0753 AC: 2317 AN: 30758

American (AMR) AF: 0.00475 AC: 162 AN: 34078

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24944

East Asian (EAS) AF: 0.0000288 AC: 1 AN: 34714

South Asian (SAS) AF: 0.000197 AC: 15 AN: 76214

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33842

Middle Eastern (MID) AF: 0.00430 AC: 22 AN: 5118

European-Non Finnish (NFE) AF: 0.000253 AC: 272 AN: 1073250

Other (OTH) AF: 0.00502 AC: 288 AN: 57342

GnomAD4 genome AF: 0.0223 AC: 3388 AN: 151640 Hom.: 137 Cov.: 31 AF XY: 0.0217 AC XY: 1608 AN XY: 74040

African (AFR) AF: 0.0772 AC: 3188 AN: 41314

American (AMR) AF: 0.00809 AC: 123 AN: 15202

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5140

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4808

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10422

Middle Eastern (MID) AF: 0.00345 AC: 1 AN: 290

European-Non Finnish (NFE) AF: 0.000530 AC: 36 AN: 67982

Other (OTH) AF: 0.0186 AC: 39 AN: 2102

Alfa AF: 0.0181 Hom.: 13

Bravo AF: 0.0249

Asia WGS AF: 0.00635 AC: 22 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	not specified (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.1
DANN	Benign	0.77
PhyloP100		0.019
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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;