chr17-59860333-A-T

Position:

• chr17-59860333-A-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_016261.4(TUBD1):​c.1351T>A​(p.Cys451Ser) 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 benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 30)
• Consequence: TUBD1 NM_016261.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.375

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.025894463).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TUBD1	NM_016261.4	c.1351T>A	p.Cys451Ser	missense_variant	9/9	ENST00000325752.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TUBD1	ENST00000325752.8	c.1351T>A	p.Cys451Ser	missense_variant	9/9	5	NM_016261.4	P1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 30

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

Jan 07, 2022

The c.1351T>A (p.C451S) alteration is located in exon 9 (coding exon 8) of the TUBD1 gene. This alteration results from a T to A substitution at nucleotide position 1351, causing the cysteine (C) at amino acid position 451 to be replaced by a serine (S). 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	0.070
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	3.5
DANN	Benign	0.48
DEOGEN2	Benign	0.012	.;T;.;.;.;.;T;.
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.086	N
LIST_S2	Benign	0.60	T;T;T;T;T;.;.;T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.026	T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-1.4	.;N;.;.;.;.;N;.
MutationTaster	Benign	1.0	N;N;N;N;N;N;N
PrimateAI	Benign	0.25	T
PROVEAN	Benign	0.25	.;N;N;N;N;N;.;N
REVEL	Benign	0.074
Sift	Benign	0.89	.;T;T;T;T;T;.;T
Sift4G	Benign	0.87	T;T;T;T;T;T;T;T
Polyphen		0.0, 0.011	.;B;B;B;.;.;B;.
Vest4		0.078
MutPred		0.31		.;Gain of disorder (P = 3e-04);.;.;.;.;Gain of disorder (P = 3e-04);.;
MVP		0.39
MPC		0.13
ClinPred		0.025	T
GERP RS		-6.1
Varity_R		0.026
gMVP		0.18

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: chr17-57937694;