NM_016261.4:c.227T>A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_016261.4(TUBD1):​c.227T>A​(p.Met76Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 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: not found (cov: 31)
• Consequence: TUBD1 NM_016261.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.26
• Publications: 0 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.35191864).

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>A	p.Met76Lys	missense	Exon 3 of 9	NP_057345.2
	TUBD1	NM_001193609.2		c.227T>A	p.Met76Lys	missense	Exon 3 of 8	NP_001180538.1
	TUBD1	NM_001193610.2		c.227T>A	p.Met76Lys	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>A	p.Met76Lys	missense	Exon 3 of 9	ENSP00000320797.3
	TUBD1	ENST00000592426.5	TSL:1	c.227T>A	p.Met76Lys	missense	Exon 2 of 8	ENSP00000468518.1
	TUBD1	ENST00000340993.10	TSL:1	c.227T>A	p.Met76Lys	missense	Exon 3 of 8	ENSP00000342399.5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 44

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Benign	-0.048	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	20
DANN	Benign	0.96
DEOGEN2	Benign	0.037	T
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.17
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.67	T
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.35	T
MetaSVM	Benign	-0.65	T
MutationAssessor	Benign	0.81	L
PhyloP100		4.3
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.16	N
REVEL	Benign	0.17
Sift	Uncertain	0.011	D
Sift4G	Uncertain	0.054	T
Polyphen		0.0020	B
Vest4		0.34
MutPred		0.82		Gain of disorder (P = 0.0173)
MVP		0.74
MPC		0.19
ClinPred		0.55	D
GERP RS		4.1
Varity_R		0.39
gMVP		0.53

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;