chr17-59890841-C-G

Position:

• chr17-59890841-C-G

Variant summary

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

The NM_016261.4(TUBD1):​c.162G>C​(p.Glu54Asp) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TUBD1 NM_016261.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.635

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=0.057510555).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TUBD1	NM_016261.4	c.162G>C	p.Glu54Asp	missense_variant	2/9	ENST00000325752.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TUBD1	ENST00000325752.8	c.162G>C	p.Glu54Asp	missense_variant	2/9	5	NM_016261.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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

Nov 06, 2023

The c.162G>C (p.E54D) alteration is located in exon 2 (coding exon 1) of the TUBD1 gene. This alteration results from a G to C substitution at nucleotide position 162, causing the glutamic acid (E) at amino acid position 54 to be replaced by an aspartic acid (D). 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	0.095
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	9.0
DANN	Uncertain	1.0
DEOGEN2	Benign	0.020	.;T;.;.;.;.;T
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.65
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.78	T;T;T;T;T;.;.
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.058	T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.64	N;N;N;N;N;N;N
MutationTaster	Benign	1.0	D;N;N;N;N;N;N
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-1.1	.;N;N;N;N;N;.
REVEL	Benign	0.075
Sift	Benign	0.26	.;T;T;T;T;T;.
Sift4G	Benign	0.49	T;T;T;T;T;T;T
Polyphen		0.0, 0.0030, 0.0010	.;B;B;B;.;.;B
Vest4		0.17
MutPred		0.46		Loss of disorder (P = 0.128);Loss of disorder (P = 0.128);Loss of disorder (P = 0.128);Loss of disorder (P = 0.128);Loss of disorder (P = 0.128);Loss of disorder (P = 0.128);Loss of disorder (P = 0.128);
MVP		0.49
MPC		0.097
ClinPred		0.24	T
GERP RS		-0.40
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.082
gMVP		0.19

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: chr17-57968202;