17-59865754-T-G

Variant names:

• chr17-59865754-T-G
• rs2645482
• NM_016261.4:c.1075+855A>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.1075+855A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.561 in 152,026 control chromosomes in the GnomAD database, including 26,074 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 0.56 (26074 hom., cov: 32)
• Consequence: TUBD1 NM_016261.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.257
• Publications: 6 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.813 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TUBD1	NM_016261.4	c.1075+855A>C		intron_variant	Intron 7 of 8	ENST00000325752.8	NP_057345.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TUBD1	ENST00000325752.8	c.1075+855A>C		intron_variant	Intron 7 of 8	5	NM_016261.4	ENSP00000320797.3

Frequencies

GnomAD3 genomes AF: 0.561 AC: 85237 AN: 151908 Hom.: 26017 Cov.: 32

Gnomad AFR AF: 0.820

Gnomad AMI AF: 0.498

Gnomad AMR AF: 0.530

Gnomad ASJ AF: 0.417

Gnomad EAS AF: 0.563

Gnomad SAS AF: 0.489

Gnomad FIN AF: 0.429

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.444

Gnomad OTH AF: 0.556

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

GnomAD4 genome AF: 0.561 AC: 85355 AN: 152026 Hom.: 26074 Cov.: 32 AF XY: 0.559 AC XY: 41533 AN XY: 74274

African (AFR) AF: 0.820 AC: 34049 AN: 41516

American (AMR) AF: 0.530 AC: 8089 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.417 AC: 1446 AN: 3468

East Asian (EAS) AF: 0.563 AC: 2904 AN: 5158

South Asian (SAS) AF: 0.487 AC: 2349 AN: 4824

European-Finnish (FIN) AF: 0.429 AC: 4515 AN: 10516

Middle Eastern (MID) AF: 0.575 AC: 169 AN: 294

European-Non Finnish (NFE) AF: 0.444 AC: 30197 AN: 67964

Other (OTH) AF: 0.561 AC: 1183 AN: 2110

Alfa AF: 0.507 Hom.: 7680

Bravo AF: 0.577

Asia WGS AF: 0.600 AC: 2089 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	3.3
DANN	Benign	0.43
PhyloP100		0.26
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: rs2645482; hg19: chr17-57943115;