17-59878393-G-C

Variant names:

• chr17-59878393-G-C
• rs12150500
• NM_016261.4:c.538-59C>G

Variant summary

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

The NM_016261.4(TUBD1):​c.538-59C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.151 in 1,229,726 control chromosomes in the GnomAD database, including 14,614 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 0.14 (1690 hom., cov: 31)
  • Exomes 𝑓: 0.15 (12924 hom.)
• Consequence: TUBD1 NM_016261.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.132
• Publications: 10 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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.162 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.538-59C>G		intron	N/A	NP_057345.2
	TUBD1	NM_001193609.2		c.538-59C>G		intron	N/A	NP_001180538.1
	TUBD1	NM_001193610.2		c.538-59C>G		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.538-59C>G		intron	N/A	ENSP00000320797.3
	TUBD1	ENST00000592426.5	TSL:1	c.538-59C>G		intron	N/A	ENSP00000468518.1
	TUBD1	ENST00000340993.10	TSL:1	c.538-59C>G		intron	N/A	ENSP00000342399.5

Frequencies

GnomAD3 genomes AF: 0.142 AC: 21605 AN: 151820 Hom.: 1692 Cov.: 31

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.266

Gnomad AMR AF: 0.160

Gnomad ASJ AF: 0.168

Gnomad EAS AF: 0.0528

Gnomad SAS AF: 0.109

Gnomad FIN AF: 0.158

Gnomad MID AF: 0.175

Gnomad NFE AF: 0.164

Gnomad OTH AF: 0.153

GnomAD4 exome AF: 0.152 AC: 163980 AN: 1077798 Hom.: 12924 Cov.: 14 AF XY: 0.151 AC XY: 82450 AN XY: 546588

African (AFR) AF: 0.105 AC: 2662 AN: 25330

American (AMR) AF: 0.149 AC: 6020 AN: 40406

Ashkenazi Jewish (ASJ) AF: 0.163 AC: 3558 AN: 21862

East Asian (EAS) AF: 0.0334 AC: 1226 AN: 36720

South Asian (SAS) AF: 0.111 AC: 8052 AN: 72856

European-Finnish (FIN) AF: 0.157 AC: 7954 AN: 50720

Middle Eastern (MID) AF: 0.178 AC: 879 AN: 4946

European-Non Finnish (NFE) AF: 0.163 AC: 126562 AN: 777616

Other (OTH) AF: 0.149 AC: 7067 AN: 47342

GnomAD4 genome AF: 0.142 AC: 21595 AN: 151928 Hom.: 1690 Cov.: 31 AF XY: 0.142 AC XY: 10564 AN XY: 74254

African (AFR) AF: 0.105 AC: 4341 AN: 41464

American (AMR) AF: 0.160 AC: 2437 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.168 AC: 583 AN: 3464

East Asian (EAS) AF: 0.0528 AC: 273 AN: 5174

South Asian (SAS) AF: 0.107 AC: 516 AN: 4812

European-Finnish (FIN) AF: 0.158 AC: 1668 AN: 10532

Middle Eastern (MID) AF: 0.183 AC: 53 AN: 290

European-Non Finnish (NFE) AF: 0.164 AC: 11164 AN: 67954

Other (OTH) AF: 0.151 AC: 318 AN: 2106

Alfa AF: 0.152 Hom.: 228

Bravo AF: 0.141

Asia WGS AF: 0.0790 AC: 273 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.0
DANN	Benign	0.67
PhyloP100		-0.13
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: rs12150500; hg19: chr17-57955754;