rs599314

Variant names:

• chr17-82770196-A-G
• rs599314
• NM_005993.5:c.582+1630A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005993.5(TBCD):​c.582+1630A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.488 in 152,030 control chromosomes in the GnomAD database, including 19,175 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.49 (19175 hom., cov: 32)
• Consequence: TBCD NM_005993.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.48
• Publications: 13 publications found

Genes affected

TBCD (HGNC:11581): (tubulin folding cofactor D) Cofactor D 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. [provided by RefSeq, Jul 2008]

TBCD Gene-Disease associations (from GenCC):

• early-onset progressive diffuse brain atrophy-microcephaly-muscle weakness-optic atrophy syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.669 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBCD	NM_005993.5	c.582+1630A>G		intron_variant	Intron 5 of 38	ENST00000355528.9	NP_005984.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBCD	ENST00000355528.9	c.582+1630A>G		intron_variant	Intron 5 of 38	1	NM_005993.5	ENSP00000347719.4

Frequencies

GnomAD3 genomes AF: 0.488 AC: 74121 AN: 151912 Hom.: 19153 Cov.: 32

Gnomad AFR AF: 0.676

Gnomad AMI AF: 0.378

Gnomad AMR AF: 0.458

Gnomad ASJ AF: 0.388

Gnomad EAS AF: 0.396

Gnomad SAS AF: 0.372

Gnomad FIN AF: 0.428

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.413

Gnomad OTH AF: 0.458

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.488 AC: 74188 AN: 152030 Hom.: 19175 Cov.: 32 AF XY: 0.485 AC XY: 36029 AN XY: 74320

African (AFR) AF: 0.676 AC: 28028 AN: 41466

American (AMR) AF: 0.457 AC: 6984 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.388 AC: 1346 AN: 3472

East Asian (EAS) AF: 0.397 AC: 2044 AN: 5152

South Asian (SAS) AF: 0.371 AC: 1784 AN: 4814

European-Finnish (FIN) AF: 0.428 AC: 4517 AN: 10566

Middle Eastern (MID) AF: 0.486 AC: 143 AN: 294

European-Non Finnish (NFE) AF: 0.413 AC: 28042 AN: 67972

Other (OTH) AF: 0.453 AC: 956 AN: 2110

Alfa AF: 0.449 Hom.: 2604

Bravo AF: 0.501

Asia WGS AF: 0.392 AC: 1365 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	7.3
DANN	Benign	0.55
PhyloP100		1.5
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs599314; hg19: chr17-80728072;