chr17-59880923-G-C

Position:

• chr17-59880923-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 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. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar 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

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TUBD1	NM_016261.4	c.508C>G	p.Gln170Glu	missense_variant	4/9	ENST00000325752.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TUBD1	ENST00000325752.8	c.508C>G	p.Gln170Glu	missense_variant	4/9	5	NM_016261.4	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 20, 2023

The c.508C>G (p.Q170E) alteration is located in exon 4 (coding exon 3) of the TUBD1 gene. This alteration results from a C to G substitution at nucleotide position 508, causing the glutamine (Q) at amino acid position 170 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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;.;.;.;T
Eigen	Uncertain	0.28
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.90	D;D;D;D;.;.
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.41	T;T;T;T;T;T
MetaSVM	Benign	-0.70	T
MutationAssessor	Benign	1.4	L;L;L;L;L;L
MutationTaster	Benign	1.0	D;D;D;D;D;D;D
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-1.1	.;N;N;N;N;.
REVEL	Benign	0.24
Sift	Benign	0.47	.;T;T;T;T;.
Sift4G	Benign	1.0	T;T;T;T;T;T
Polyphen		0.0080, 0.0060	.;B;B;.;.;B
Vest4		0.49
MutPred		0.64		Gain of ubiquitination at K167 (P = 0.1103);Gain of ubiquitination at K167 (P = 0.1103);Gain of ubiquitination at K167 (P = 0.1103);Gain of ubiquitination at K167 (P = 0.1103);Gain of ubiquitination at K167 (P = 0.1103);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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-57958284;