rs3785513

Variant names:

• chr17-82928872-G-A
• rs3785513
• NM_005993.5:c.2694-241G>A

Your query was ambiguous. Multiple possible variants found:

• chr17-82928872-G-A
• chr17-82928872-G-T

Variant summary

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

The NM_005993.5(TBCD):​c.2694-241G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.363 in 151,968 control chromosomes in the GnomAD database, including 11,011 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 0.36 (11011 hom., cov: 32)
• Consequence: TBCD NM_005993.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.83
• Publications: 7 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: Labcorp Genetics (formerly Invitae), ClinGen, G2P, Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.539 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005993.5. 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
	TBCD	NM_005993.5	MANE Select	c.2694-241G>A		intron	N/A	NP_005984.3
	TBCD	NM_001411101.1		c.2643-241G>A		intron	N/A	NP_001398030.1	A0A804HLI2
	TBCD	NM_001411102.1		c.2613-241G>A		intron	N/A	NP_001398031.1	A0A804HJ32

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBCD	ENST00000355528.9	TSL:1 MANE Select	c.2694-241G>A		intron	N/A	ENSP00000347719.4	Q9BTW9-1
	TBCD	ENST00000571796.5	TSL:1	n.1352-241G>A		intron	N/A
	TBCD	ENST00000576677.6	TSL:1	n.1823-241G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.363 AC: 55054 AN: 151850 Hom.: 10974 Cov.: 32

Gnomad AFR AF: 0.544

Gnomad AMI AF: 0.317

Gnomad AMR AF: 0.293

Gnomad ASJ AF: 0.284

Gnomad EAS AF: 0.428

Gnomad SAS AF: 0.327

Gnomad FIN AF: 0.253

Gnomad MID AF: 0.303

Gnomad NFE AF: 0.287

Gnomad OTH AF: 0.368

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

GnomAD4 genome AF: 0.363 AC: 55147 AN: 151968 Hom.: 11011 Cov.: 32 AF XY: 0.362 AC XY: 26916 AN XY: 74282

African (AFR) AF: 0.545 AC: 22538 AN: 41388

American (AMR) AF: 0.293 AC: 4471 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.284 AC: 987 AN: 3472

East Asian (EAS) AF: 0.428 AC: 2206 AN: 5160

South Asian (SAS) AF: 0.328 AC: 1580 AN: 4816

European-Finnish (FIN) AF: 0.253 AC: 2672 AN: 10572

Middle Eastern (MID) AF: 0.301 AC: 88 AN: 292

European-Non Finnish (NFE) AF: 0.287 AC: 19530 AN: 67976

Other (OTH) AF: 0.373 AC: 786 AN: 2106

Alfa AF: 0.338 Hom.: 1606

Bravo AF: 0.374

Asia WGS AF: 0.374 AC: 1300 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.6
DANN	Benign	0.51
PhyloP100		-2.8
PromoterAI		-0.062	Neutral
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: rs3785513; hg19: chr17-80886748;