17-59888370-G-A

Variant names:

• chr17-59888370-G-A
• rs1296279
• NM_016261.4:c.173-2140C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016261.4(TUBD1):​c.173-2140C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 152,114 control chromosomes in the GnomAD database, including 2,469 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.17 (2469 hom., cov: 32)
• Consequence: TUBD1 NM_016261.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.207
• Publications: 11 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 (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.375 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.173-2140C>T		intron	N/A	NP_057345.2
	TUBD1	NM_001193609.2		c.173-2140C>T		intron	N/A	NP_001180538.1
	TUBD1	NM_001193610.2		c.173-2140C>T		intron	N/A	NP_001180539.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TUBD1	ENST00000325752.8	TSL:5 MANE Select	c.173-2140C>T		intron	N/A	ENSP00000320797.3
	TUBD1	ENST00000592426.5	TSL:1	c.173-2140C>T		intron	N/A	ENSP00000468518.1
	TUBD1	ENST00000340993.10	TSL:1	c.173-2140C>T		intron	N/A	ENSP00000342399.5

Frequencies

GnomAD3 genomes AF: 0.168 AC: 25493 AN: 151996 Hom.: 2460 Cov.: 32

Gnomad AFR AF: 0.0956

Gnomad AMI AF: 0.165

Gnomad AMR AF: 0.158

Gnomad ASJ AF: 0.134

Gnomad EAS AF: 0.389

Gnomad SAS AF: 0.264

Gnomad FIN AF: 0.176

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.191

Gnomad OTH AF: 0.168

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.168 AC: 25518 AN: 152114 Hom.: 2469 Cov.: 32 AF XY: 0.169 AC XY: 12553 AN XY: 74358

African (AFR) AF: 0.0955 AC: 3967 AN: 41536

American (AMR) AF: 0.157 AC: 2399 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.134 AC: 465 AN: 3470

East Asian (EAS) AF: 0.389 AC: 2004 AN: 5156

South Asian (SAS) AF: 0.264 AC: 1273 AN: 4830

European-Finnish (FIN) AF: 0.176 AC: 1857 AN: 10578

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.191 AC: 13004 AN: 68002

Other (OTH) AF: 0.178 AC: 374 AN: 2104

Alfa AF: 0.177 Hom.: 702

Bravo AF: 0.159

Asia WGS AF: 0.354 AC: 1230 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	7.8
DANN	Benign	0.58
PhyloP100		0.21
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: rs1296279; hg19: chr17-57965731;