NM_015279.2:c.644A>C

Variant names:

• chr12-64836539-A-C
• rs563733138
• NM_015279.2:c.644A>C

Variant summary

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

The NM_015279.2(TBC1D30):​c.644A>C​(p.Asn215Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. N215S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: TBC1D30 NM_015279.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.97
• Publications: 0 publications found

Genes affected

TBC1D30 (HGNC:29164): (TBC1 domain family member 30) Enables GTPase activator activity and small GTPase binding activity. Involved in negative regulation of cilium assembly and positive regulation of GTPase activity. Located in ciliary basal body; cytosol; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000288591 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015279.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBC1D30	NM_015279.2	MANE Select	c.644A>C	p.Asn215Thr	missense	Exon 6 of 12	NP_056094.1	Q9Y2I9-2
	TBC1D30	NM_001330186.2		c.644A>C	p.Asn215Thr	missense	Exon 6 of 12	NP_001317115.1
	TBC1D30	NM_001330187.2		c.302A>C	p.Asn101Thr	missense	Exon 8 of 14	NP_001317116.1	F8VZ81

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBC1D30	ENST00000539867.6	TSL:1 MANE Select	c.644A>C	p.Asn215Thr	missense	Exon 6 of 12	ENSP00000440207.1	Q9Y2I9-2
	TBC1D30	ENST00000542120.6	TSL:1	c.1133A>C	p.Asn378Thr	missense	Exon 7 of 13	ENSP00000440640.2	Q9Y2I9-1
	ENSG00000288591	ENST00000674281.1		n.302A>C		non_coding_transcript_exon	Exon 8 of 17	ENSP00000501395.1	F8VZ81

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

Alfa AF: 0.0000407 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.62
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.083	T
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.016	T
MetaRNN	Uncertain	0.45	T
MetaSVM	Benign	-1.2	T
PhyloP100		6.0
PrimateAI	Pathogenic	0.82	D
PROVEAN	Pathogenic	-4.4	D
REVEL	Benign	0.26
Sift	Benign	0.051	T
Sift4G	Uncertain	0.0070	D
Vest4		0.56
MVP		0.32
ClinPred		0.99	D
GERP RS		5.3
gMVP		0.75
Mutation Taster		=54/46	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: rs563733138; hg19: chr12-65230319;