rs1292053

Positions:

• chr17-59886176-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016261.4(TUBD1):​c.227T>C​(p.Met76Thr) variant causes a missense change. The variant allele was found at a frequency of 0.445 in 1,613,168 control chromosomes in the GnomAD database, including 161,267 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.46 (16348 hom., cov: 31)
  • Exomes 𝑓: 0.44 (144919 hom.)
• Consequence: TUBD1 NM_016261.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.26

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.2314974E-4).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.543 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TUBD1	NM_016261.4	c.227T>C	p.Met76Thr	missense_variant	3/9	ENST00000325752.8	NP_057345.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TUBD1	ENST00000325752.8	c.227T>C	p.Met76Thr	missense_variant	3/9	5	NM_016261.4	ENSP00000320797	P1

Frequencies

GnomAD3 genomes AF: 0.463 AC: 70196 AN: 151584 Hom.: 16336 Cov.: 31

Gnomad AFR AF: 0.487

Gnomad AMI AF: 0.499

Gnomad AMR AF: 0.489

Gnomad ASJ AF: 0.417

Gnomad EAS AF: 0.561

Gnomad SAS AF: 0.427

Gnomad FIN AF: 0.429

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.444

Gnomad OTH AF: 0.492

GnomAD3 exomes AF: 0.447 AC: 112303 AN: 251154 Hom.: 25550 AF XY: 0.445 AC XY: 60391 AN XY: 135744

Gnomad AFR exome AF: 0.483

Gnomad AMR exome AF: 0.414

Gnomad ASJ exome AF: 0.423

Gnomad EAS exome AF: 0.577

Gnomad SAS exome AF: 0.432

Gnomad FIN exome AF: 0.424

Gnomad NFE exome AF: 0.442

Gnomad OTH exome AF: 0.447

GnomAD4 exome AF: 0.443 AC: 647707 AN: 1461466 Hom.: 144919 Cov.: 44 AF XY: 0.443 AC XY: 321741 AN XY: 727054

Gnomad4 AFR exome AF: 0.494

Gnomad4 AMR exome AF: 0.421

Gnomad4 ASJ exome AF: 0.421

Gnomad4 EAS exome AF: 0.584

Gnomad4 SAS exome AF: 0.430

Gnomad4 FIN exome AF: 0.432

Gnomad4 NFE exome AF: 0.439

Gnomad4 OTH exome AF: 0.450

GnomAD4 genome AF: 0.463 AC: 70245 AN: 151702 Hom.: 16348 Cov.: 31 AF XY: 0.463 AC XY: 34295 AN XY: 74094

Gnomad4 AFR AF: 0.487

Gnomad4 AMR AF: 0.489

Gnomad4 ASJ AF: 0.417

Gnomad4 EAS AF: 0.560

Gnomad4 SAS AF: 0.425

Gnomad4 FIN AF: 0.429

Gnomad4 NFE AF: 0.444

Gnomad4 OTH AF: 0.498

Alfa AF: 0.450 Hom.: 39131

Bravo AF: 0.466

TwinsUK AF: 0.440 AC: 1632

ALSPAC AF: 0.449 AC: 1732

ESP6500AA AF: 0.482 AC: 2123

ESP6500EA AF: 0.436 AC: 3751

ExAC AF: 0.446 AC: 54148

Asia WGS AF: 0.545 AC: 1896 AN: 3478

EpiCase AF: 0.454

EpiControl AF: 0.452

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	13
DANN	Benign	0.60
DEOGEN2	Benign	0.015	.;T;.;.;.;T;T
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.45
FATHMM_MKL	Benign	0.46	N
LIST_S2	Benign	0.15	T;T;T;T;.;.;T
MetaRNN	Benign	0.00012	T;T;T;T;T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	-1.4	N;N;N;N;N;N;.
MutationTaster	Benign	1.0	P;P;P;P;P;P;P
PrimateAI	Benign	0.39	T
PROVEAN	Benign	3.6	.;N;N;N;N;.;.
REVEL	Benign	0.10
Sift	Benign	1.0	.;T;T;T;T;.;.
Sift4G	Benign	0.78	T;T;T;T;T;T;.
Polyphen		0.0	.;B;B;.;.;B;.
Vest4		0.049
MPC		0.12
ClinPred		0.0010	T
GERP RS		4.1
Varity_R		0.032
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

LitVar

Other links and lift over

dbSNP: rs1292053; hg19: chr17-57963537; COSMIC: COSV57872241; COSMIC: COSV57872241;