chr17-42666681-A-T

Variant names:

• chr17-42666681-A-T
• rs1046097
• NM_016437.3:c.1237A>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016437.3(TUBG2):​c.1237A>T​(p.Met413Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,876 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M413V) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: TUBG2 NM_016437.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.34
• Publications: 42 publications found

Genes affected

TUBG2 (HGNC:12419): (tubulin gamma 2) Predicted to enable GTP binding activity. Predicted to be a structural constituent of cytoskeleton. Predicted to be involved in microtubule cytoskeleton organization and mitotic sister chromatid segregation. Located in microtubule. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24618924).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TUBG2	NM_016437.3	c.1237A>T	p.Met413Leu	missense_variant	Exon 11 of 11	ENST00000251412.8	NP_057521.1
TUBG2	NM_001320509.2	c.1264A>T	p.Met422Leu	missense_variant	Exon 12 of 12		NP_001307438.1
TUBG2	XM_047435757.1	c.778A>T	p.Met260Leu	missense_variant	Exon 8 of 8		XP_047291713.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TUBG2	ENST00000251412.8	c.1237A>T	p.Met413Leu	missense_variant	Exon 11 of 11	1	NM_016437.3	ENSP00000251412.6
TUBG2	ENST00000588870.1	n.1635A>T		non_coding_transcript_exon_variant	Exon 9 of 9	1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461876 Hom.: 0 Cov.: 59 AF XY: 0.00000275 AC XY: 2 AN XY: 727240

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1112006

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.0016	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	19
DANN	Benign	0.90
DEOGEN2	Benign	0.11	T
Eigen	Benign	0.083
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.25	T
MetaSVM	Uncertain	-0.026	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		7.3
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.24
Sift	Benign	0.62	T
Sift4G	Benign	0.29	T
Polyphen		0.0	B
Vest4		0.18
MutPred		0.31		Loss of ubiquitination at K410 (P = 0.0486);
MVP		0.90
MPC		0.78
ClinPred		0.86	D
GERP RS		5.1
Varity_R		0.25
gMVP		0.42
Mutation Taster		=75/25	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1046097; hg19: chr17-40818699;