rs2040455664

Variant names:

• chr17-59880923-G-C
• rs2040455664
• NM_016261.4:c.508C>G

Your query was ambiguous. Multiple possible variants found:

• chr17-59880923-G-C
• chr17-59880923-G-A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_016261.4(TUBD1):​c.508C>G​(p.Gln170Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q170H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: TUBD1 NM_016261.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.24
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.40897003).

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.508C>G	p.Gln170Glu	missense	Exon 4 of 9	NP_057345.2	Q9UJT1-1
	TUBD1	NM_001193609.2		c.508C>G	p.Gln170Glu	missense	Exon 4 of 8	NP_001180538.1	Q9UJT1-2
	TUBD1	NM_001193610.2		c.508C>G	p.Gln170Glu	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.508C>G	p.Gln170Glu	missense	Exon 4 of 9	ENSP00000320797.3	Q9UJT1-1
	TUBD1	ENST00000592426.5	TSL:1	c.508C>G	p.Gln170Glu	missense	Exon 3 of 8	ENSP00000468518.1	Q9UJT1-1
	TUBD1	ENST00000340993.10	TSL:1	c.508C>G	p.Gln170Glu	missense	Exon 4 of 8	ENSP00000342399.5	Q9UJT1-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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	0.13
BayesDel_addAF	Uncertain	0.017	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.045	T
Eigen	Uncertain	0.28
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.41	T
MetaSVM	Benign	-0.70	T
MutationAssessor	Benign	1.4	L
PhyloP100		9.2
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.24
Sift	Benign	0.47	T
Sift4G	Benign	1.0	T
Polyphen		0.0080	B
Vest4		0.49
MutPred		0.64		Gain of ubiquitination at K167 (P = 0.1103)
MVP		0.75
MPC		0.14
ClinPred		0.90	D
GERP RS		6.1
Varity_R		0.41
gMVP		0.74

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: rs2040455664; hg19: chr17-57958284;