rs3744161

Variant names:

• chr17-82870181-G-A
• rs3744161
• NM_005993.5:c.1319-43G>A

Your query was ambiguous. Multiple possible variants found:

• chr17-82870181-G-A
• chr17-82870181-G-C
• chr17-82870181-G-T

Variant summary

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

The NM_005993.5(TBCD):​c.1319-43G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.563 in 1,609,494 control chromosomes in the GnomAD database, including 258,531 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.52 (21529 hom., cov: 33)
  • Exomes 𝑓: 0.57 (237002 hom.)
• Consequence: TBCD NM_005993.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.484
• Publications: 10 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: ClinGen, PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P, Orphanet

LOC124904096 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 17-82870181-G-A is Benign according to our data. Variant chr17-82870181-G-A is described in ClinVar as Benign. ClinVar VariationId is 1265397.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.69 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.1319-43G>A		intron	N/A	NP_005984.3
	TBCD	NM_001411101.1		c.1268-43G>A		intron	N/A	NP_001398030.1	A0A804HLI2
	TBCD	NM_001411102.1		c.1319-43G>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.1319-43G>A		intron	N/A	ENSP00000347719.4	Q9BTW9-1
	TBCD	ENST00000684760.1		c.1319-43G>A		intron	N/A	ENSP00000507696.1	A0A804HJY5
	TBCD	ENST00000684349.1		c.1319-43G>A		intron	N/A	ENSP00000508067.1	A0A804HKT8

Frequencies

GnomAD3 genomes AF: 0.522 AC: 79274 AN: 151930 Hom.: 21511 Cov.: 33

Gnomad AFR AF: 0.364

Gnomad AMI AF: 0.752

Gnomad AMR AF: 0.587

Gnomad ASJ AF: 0.512

Gnomad EAS AF: 0.710

Gnomad SAS AF: 0.463

Gnomad FIN AF: 0.602

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.578

Gnomad OTH AF: 0.535

GnomAD2 exomes AF: 0.563 AC: 137718 AN: 244402 AF XY: 0.558

Gnomad AFR exome AF: 0.355

Gnomad AMR exome AF: 0.628

Gnomad ASJ exome AF: 0.517

Gnomad EAS exome AF: 0.727

Gnomad FIN exome AF: 0.595

Gnomad NFE exome AF: 0.573

Gnomad OTH exome AF: 0.556

GnomAD4 exome AF: 0.567 AC: 826919 AN: 1457446 Hom.: 237002 Cov.: 40 AF XY: 0.565 AC XY: 409692 AN XY: 725248

African (AFR) AF: 0.352 AC: 11768 AN: 33424

American (AMR) AF: 0.617 AC: 27550 AN: 44628

Ashkenazi Jewish (ASJ) AF: 0.516 AC: 13467 AN: 26104

East Asian (EAS) AF: 0.741 AC: 29414 AN: 39682

South Asian (SAS) AF: 0.464 AC: 40033 AN: 86196

European-Finnish (FIN) AF: 0.592 AC: 29537 AN: 49918

Middle Eastern (MID) AF: 0.463 AC: 2669 AN: 5764

European-Non Finnish (NFE) AF: 0.575 AC: 639174 AN: 1111408

Other (OTH) AF: 0.552 AC: 33307 AN: 60322

GnomAD4 genome AF: 0.522 AC: 79335 AN: 152048 Hom.: 21529 Cov.: 33 AF XY: 0.524 AC XY: 38975 AN XY: 74324

African (AFR) AF: 0.364 AC: 15097 AN: 41476

American (AMR) AF: 0.587 AC: 8972 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.512 AC: 1777 AN: 3470

East Asian (EAS) AF: 0.710 AC: 3657 AN: 5154

South Asian (SAS) AF: 0.465 AC: 2239 AN: 4820

European-Finnish (FIN) AF: 0.602 AC: 6357 AN: 10564

Middle Eastern (MID) AF: 0.466 AC: 137 AN: 294

European-Non Finnish (NFE) AF: 0.578 AC: 39280 AN: 67972

Other (OTH) AF: 0.539 AC: 1133 AN: 2102

Alfa AF: 0.518 Hom.: 5942

Bravo AF: 0.516

Asia WGS AF: 0.542 AC: 1887 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Early-onset progressive diffuse brain atrophy-microcephaly-muscle weakness-optic atrophy syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.4
DANN	Benign	0.75
PhyloP100		-0.48
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	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: rs3744161; hg19: chr17-80828057; COSMIC: COSV62801426;