17-59886176-A-G

Variant names:

• chr17-59886176-A-G
• rs1292053
• NM_016261.4:c.227T>C

Variant summary

Our verdict is Benign. The variant received -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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 102 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016261.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TUBD1	NM_016261.4	MANE Select	c.227T>C	p.Met76Thr	missense	Exon 3 of 9	NP_057345.2
	TUBD1	NM_001193609.2		c.227T>C	p.Met76Thr	missense	Exon 3 of 8	NP_001180538.1
	TUBD1	NM_001193610.2		c.227T>C	p.Met76Thr	missense	Exon 3 of 8	NP_001180539.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TUBD1	ENST00000325752.8	TSL:5 MANE Select	c.227T>C	p.Met76Thr	missense	Exon 3 of 9	ENSP00000320797.3
	TUBD1	ENST00000592426.5	TSL:1	c.227T>C	p.Met76Thr	missense	Exon 2 of 8	ENSP00000468518.1
	TUBD1	ENST00000340993.10	TSL:1	c.227T>C	p.Met76Thr	missense	Exon 3 of 8	ENSP00000342399.5

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

GnomAD2 exomes AF: 0.447 AC: 112303 AN: 251154 AF XY: 0.445

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 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

African (AFR) AF: 0.494 AC: 16517 AN: 33456

American (AMR) AF: 0.421 AC: 18824 AN: 44680

Ashkenazi Jewish (ASJ) AF: 0.421 AC: 10999 AN: 26128

East Asian (EAS) AF: 0.584 AC: 23160 AN: 39688

South Asian (SAS) AF: 0.430 AC: 37066 AN: 86202

European-Finnish (FIN) AF: 0.432 AC: 23074 AN: 53406

Middle Eastern (MID) AF: 0.507 AC: 2924 AN: 5766

European-Non Finnish (NFE) AF: 0.439 AC: 487982 AN: 1111766

Other (OTH) AF: 0.450 AC: 27161 AN: 60374

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

African (AFR) AF: 0.487 AC: 20113 AN: 41340

American (AMR) AF: 0.489 AC: 7420 AN: 15176

Ashkenazi Jewish (ASJ) AF: 0.417 AC: 1446 AN: 3470

East Asian (EAS) AF: 0.560 AC: 2891 AN: 5162

South Asian (SAS) AF: 0.425 AC: 2049 AN: 4818

European-Finnish (FIN) AF: 0.429 AC: 4503 AN: 10496

Middle Eastern (MID) AF: 0.524 AC: 154 AN: 294

European-Non Finnish (NFE) AF: 0.444 AC: 30168 AN: 67934

Other (OTH) AF: 0.498 AC: 1048 AN: 2104

Alfa AF: 0.451 Hom.: 75108

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 v4.9

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
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.45
FATHMM_MKL	Benign	0.46	N
LIST_S2	Benign	0.15	T
MetaRNN	Benign	0.00012	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	-1.4	N
PhyloP100		4.3
PrimateAI	Benign	0.39	T
PROVEAN	Benign	3.6	N
REVEL	Benign	0.10
Sift	Benign	1.0	T
Sift4G	Benign	0.78	T
Polyphen		0.0	B
Vest4		0.049
MPC		0.12
ClinPred		0.0010	T
GERP RS		4.1
Varity_R		0.032
gMVP		0.18
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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