17-59881082-C-T

Variant names:

• chr17-59881082-C-T
• NM_016261.4:c.349G>A

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_016261.4(TUBD1):​c.349G>A​(p.Glu117Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,820 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: TUBD1 NM_016261.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.29
• Publications: 0 publications found

Genes affected

TUBD1 (HGNC:16811): (tubulin delta 1) Predicted to enable GTP binding activity. Predicted to be a structural constituent of cytoskeleton. Predicted to be involved in microtubule cytoskeleton organization; mitotic cell cycle; and positive regulation of smoothened signaling pathway. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.938

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016261.4. 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
	TUBD1	NM_016261.4	MANE Select	c.349G>A	p.Glu117Lys	missense	Exon 4 of 9	NP_057345.2	Q9UJT1-1
	TUBD1	NM_001193609.2		c.349G>A	p.Glu117Lys	missense	Exon 4 of 8	NP_001180538.1	Q9UJT1-2
	TUBD1	NM_001193610.2		c.349G>A	p.Glu117Lys	missense	Exon 4 of 8	NP_001180539.1	Q9UJT1-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TUBD1	ENST00000325752.8	TSL:5 MANE Select	c.349G>A	p.Glu117Lys	missense	Exon 4 of 9	ENSP00000320797.3	Q9UJT1-1
	TUBD1	ENST00000592426.5	TSL:1	c.349G>A	p.Glu117Lys	missense	Exon 3 of 8	ENSP00000468518.1	Q9UJT1-1
	TUBD1	ENST00000340993.10	TSL:1	c.349G>A	p.Glu117Lys	missense	Exon 4 of 8	ENSP00000342399.5	Q9UJT1-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461820 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727208

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39684

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53406

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111978

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000611 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Uncertain	25
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.26	T
Eigen	Pathogenic	0.77
Eigen_PC	Pathogenic	0.80
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.95	D
M_CAP	Uncertain	0.13	D
MetaRNN	Pathogenic	0.94	D
MetaSVM	Uncertain	0.11	D
MutationAssessor	Pathogenic	3.1	M
PhyloP100		7.3
PrimateAI	Uncertain	0.52	T
PROVEAN	Uncertain	-2.9	D
REVEL	Uncertain	0.52
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.042	D
Polyphen		0.87	P
Vest4		0.55
MutPred		0.84		Gain of methylation at E117 (P = 0.0067)
MVP		0.93
MPC		0.38
ClinPred		0.99	D
GERP RS		6.1
Varity_R		0.89
gMVP		0.46
Mutation Taster		=52/48	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.27		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.27		Position offset: 28

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

hg19: chr17-57958443;