chr1-235367487-T-C

Variant names:

• chr1-235367487-T-C
• rs55980101
• NM_003193.5:c.-49T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003193.5(TBCE):​c.-49T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0333 in 153,100 control chromosomes in the GnomAD database, including 189 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.033 (189 hom., cov: 32)
  • Exomes 𝑓: 0.0099 (0 hom.)
• Consequence: TBCE NM_003193.5 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.548
• Publications: 4 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]

TBCE Gene-Disease associations (from GenCC):

• hypoparathyroidism-retardation-dysmorphism syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P
• early-onset progressive diffuse brain atrophy-microcephaly-muscle weakness-optic atrophy syndrome

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• encephalopathy, progressive, with amyotrophy and optic atrophy

  Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: Ambry Genetics, ClinGen, G2P
• autosomal recessive Kenny-Caffey syndrome

  Inheritance: AR Classification: MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet

ENSG00000285053 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 1-235367487-T-C is Benign according to our data. Variant chr1-235367487-T-C is described in ClinVar as Benign. ClinVar VariationId is 296288.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0916 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003193.5. 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.-49T>C		5_prime_UTR	Exon 1 of 17	NP_003184.1	Q15813-1
	TBCE	NM_001287801.2		c.-49T>C		5_prime_UTR	Exon 1 of 18	NP_001274730.1	Q15813-2
	TBCE	NM_001079515.3		c.-97T>C		5_prime_UTR	Exon 1 of 17	NP_001072983.1	Q15813-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBCE	ENST00000642610.2	MANE Select	c.-49T>C		5_prime_UTR	Exon 1 of 17	ENSP00000494796.1	Q15813-1
	ENSG00000285053	ENST00000647186.1		c.-49T>C		5_prime_UTR	Exon 3 of 19	ENSP00000494775.1
	TBCE	ENST00000366601.8	TSL:1	c.-49T>C		5_prime_UTR	Exon 1 of 15	ENSP00000355560.4	A0A2U3TZJ6

Frequencies

GnomAD3 genomes AF: 0.0334 AC: 5075 AN: 152172 Hom.: 188 Cov.: 32

Gnomad AFR AF: 0.0941

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0223

Gnomad ASJ AF: 0.00346

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00331

Gnomad FIN AF: 0.00687

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.00963

Gnomad OTH AF: 0.0315

GnomAD4 exome AF: 0.00988 AC: 8 AN: 810 Hom.: 0 Cov.: 0 AF XY: 0.00923 AC XY: 5 AN XY: 542

African (AFR) AF: 0.143 AC: 2 AN: 14

American (AMR) AF: 0.00 AC: 0 AN: 6

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 12

South Asian (SAS) AF: 0.00 AC: 0 AN: 4

European-Finnish (FIN) AF: 0.00694 AC: 3 AN: 432

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4

European-Non Finnish (NFE) AF: 0.00949 AC: 3 AN: 316

Other (OTH) AF: 0.00 AC: 0 AN: 22

GnomAD4 genome AF: 0.0334 AC: 5083 AN: 152290 Hom.: 189 Cov.: 32 AF XY: 0.0319 AC XY: 2376 AN XY: 74466

African (AFR) AF: 0.0940 AC: 3910 AN: 41574

American (AMR) AF: 0.0222 AC: 339 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00346 AC: 12 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00331 AC: 16 AN: 4828

European-Finnish (FIN) AF: 0.00687 AC: 73 AN: 10622

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.00963 AC: 655 AN: 68008

Other (OTH) AF: 0.0312 AC: 66 AN: 2114

Alfa AF: 0.0188 Hom.: 37

Bravo AF: 0.0379

Asia WGS AF: 0.00895 AC: 31 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Hypoparathyroidism-retardation-dysmorphism syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.6
DANN	Benign	0.55
PhyloP100		-0.55
PromoterAI		0.28	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1
Mutation Taster		=300/0	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: rs55980101; hg19: chr1-235530802;