17-59860424-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_016261.4(TUBD1):c.1260A>C(p.Lys420Asn) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 30)
• Consequence: TUBD1 NM_016261.4 missense, splice_region
• Scores: Splicing: ADA: 0.0002340
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.994

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TUBD1	NM_016261.4	c.1260A>C	p.Lys420Asn	missense_variant, splice_region_variant	9/9	ENST00000325752.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TUBD1	ENST00000325752.8	c.1260A>C	p.Lys420Asn	missense_variant, splice_region_variant	9/9	5	NM_016261.4	P1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 26

GnomAD4 genome Cov.: 30

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

Jul 09, 2021

The c.1260A>C (p.K420N) alteration is located in exon 9 (coding exon 8) of the TUBD1 gene. This alteration results from a A to C substitution at nucleotide position 1260, causing the lysine (K) at amino acid position 420 to be replaced by an asparagine (N). 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	Pathogenic	0.74
BayesDel_addAF	Uncertain	0.018	T
BayesDel_noAF	Benign	-0.21
Cadd	Benign	21
Dann	Uncertain	0.99
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.28
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Uncertain	0.93	D;D;D;D;.;.;D
M_CAP	Benign	0.080	D
MetaRNN	Uncertain	0.49	T;T;T;T;T;T;T
MetaSVM	Benign	-0.53	T
MutationTaster	Benign	1.0	D;D;D;D;D;N;N
PrimateAI	Uncertain	0.56	T
Sift4G	Benign	0.093	T;T;D;T;T;T;D
Polyphen		0.031, 0.99, 0.11	.;B;D;B;.;B;.
Vest4		0.55
MutPred		0.69		.;Loss of methylation at K420 (P = 0.0126);.;.;.;Loss of methylation at K420 (P = 0.0126);.;
MVP		0.82
MPC		0.13
ClinPred		0.95	D
GERP RS		0.82
Varity_R		0.30
gMVP		0.72

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00023
dbscSNV1_RF	Benign	0.026
SpliceAI score (max)		0.010		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: chr17-57937785;