rs1292053

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr17-59886176-A-C
• chr17-59886176-A-G
• chr17-59886176-A-T

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>G​(p.Met76Arg) 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. 14/22 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=0.30910176).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TUBD1	NM_016261.4	c.227T>G	p.Met76Arg	missense_variant	Exon 3 of 9	ENST00000325752.8	NP_057345.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TUBD1	ENST00000325752.8	c.227T>G	p.Met76Arg	missense_variant	Exon 3 of 9	5	NM_016261.4	ENSP00000320797.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 44

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	-0.038	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.028	.;T;.;.;.;T;T
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.16
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.67	T;T;T;T;.;.;T
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.31	T;T;T;T;T;T;T
MetaSVM	Benign	-0.63	T
MutationAssessor	Benign	0.81	L;L;L;L;L;L;.
PhyloP100		4.3
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.32	.;N;N;N;N;.;.
REVEL	Benign	0.16
Sift	Uncertain	0.0060	.;D;D;D;D;.;.
Sift4G	Uncertain	0.032	D;D;D;D;D;D;.
Polyphen		0.037, 0.0080	.;B;B;.;.;B;.
Vest4		0.36
MutPred		0.80		Loss of ubiquitination at K79 (P = 0.022);Loss of ubiquitination at K79 (P = 0.022);Loss of ubiquitination at K79 (P = 0.022);Loss of ubiquitination at K79 (P = 0.022);Loss of ubiquitination at K79 (P = 0.022);Loss of ubiquitination at K79 (P = 0.022);.;
MVP		0.74
MPC		0.21
ClinPred		0.54	D
GERP RS		4.1
Varity_R		0.46
gMVP		0.60

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;