17-59881060-C-A

Variant names:

• chr17-59881060-C-A
• rs773282613
• NM_016261.4:c.371G>T

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.371G>T​(p.Arg124Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R124Q) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: TUBD1 NM_016261.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.816
• Publications: 1 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, 0.846

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.371G>T	p.Arg124Leu	missense	Exon 4 of 9	NP_057345.2	Q9UJT1-1
	TUBD1	NM_001193609.2		c.371G>T	p.Arg124Leu	missense	Exon 4 of 8	NP_001180538.1	Q9UJT1-2
	TUBD1	NM_001193610.2		c.371G>T	p.Arg124Leu	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.371G>T	p.Arg124Leu	missense	Exon 4 of 9	ENSP00000320797.3	Q9UJT1-1
	TUBD1	ENST00000592426.5	TSL:1	c.371G>T	p.Arg124Leu	missense	Exon 3 of 8	ENSP00000468518.1	Q9UJT1-1
	TUBD1	ENST00000340993.10	TSL:1	c.371G>T	p.Arg124Leu	missense	Exon 4 of 8	ENSP00000342399.5	Q9UJT1-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Uncertain	0.064	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.41	T
Eigen	Uncertain	0.24
Eigen_PC	Benign	0.20
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.89	D
M_CAP	Pathogenic	0.46	D
MetaRNN	Pathogenic	0.85	D
MetaSVM	Uncertain	0.22	D
MutationAssessor	Pathogenic	3.8	H
PhyloP100		0.82
PrimateAI	Benign	0.22	T
PROVEAN	Pathogenic	-4.5	D
REVEL	Uncertain	0.64
Sift	Uncertain	0.0090	D
Sift4G	Uncertain	0.0080	D
Polyphen		0.99	D
Vest4		0.59
MutPred		0.76		Gain of catalytic residue at R124 (P = 0.0019)
MVP		0.89
MPC		0.52
ClinPred		0.99	D
GERP RS		3.8
Varity_R		0.48
gMVP		0.56

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs773282613; hg19: chr17-57958421;