rs563733138

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr12-64836539-A-G
• chr12-64836539-A-C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_015279.2(TBC1D30):​c.644A>G​(p.Asn215Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000326 in 1,535,902 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000033 (0 hom.)
• Consequence: TBC1D30 NM_015279.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.24361128).

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>G	p.Asn215Ser	missense	Exon 6 of 12	NP_056094.1	Q9Y2I9-2
	TBC1D30	NM_001330186.2		c.644A>G	p.Asn215Ser	missense	Exon 6 of 12	NP_001317115.1
	TBC1D30	NM_001330187.2		c.302A>G	p.Asn101Ser	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>G	p.Asn215Ser	missense	Exon 6 of 12	ENSP00000440207.1	Q9Y2I9-2
	TBC1D30	ENST00000542120.6	TSL:1	c.1133A>G	p.Asn378Ser	missense	Exon 7 of 13	ENSP00000440640.2	Q9Y2I9-1
	ENSG00000288591	ENST00000674281.1		n.302A>G		non_coding_transcript_exon	Exon 8 of 17	ENSP00000501395.1	F8VZ81

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 152156 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000583 AC: 8 AN: 137206 AF XY: 0.0000536

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000123

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000952

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000371

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000325 AC: 45 AN: 1383746 Hom.: 0 Cov.: 30 AF XY: 0.0000381 AC XY: 26 AN XY: 682806

African (AFR) AF: 0.0000317 AC: 1 AN: 31588

American (AMR) AF: 0.0000840 AC: 3 AN: 35696

Ashkenazi Jewish (ASJ) AF: 0.0000397 AC: 1 AN: 25178

East Asian (EAS) AF: 0.0000560 AC: 2 AN: 35720

South Asian (SAS) AF: 0.000202 AC: 16 AN: 79216

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33896

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5698

European-Non Finnish (NFE) AF: 0.0000185 AC: 20 AN: 1078852

Other (OTH) AF: 0.0000345 AC: 2 AN: 57902

GnomAD4 genome AF: 0.0000329 AC: 5 AN: 152156 Hom.: 0 Cov.: 31 AF XY: 0.0000269 AC XY: 2 AN XY: 74340

African (AFR) AF: 0.0000241 AC: 1 AN: 41428

American (AMR) AF: 0.00 AC: 0 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000578 AC: 3 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000227

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.56
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.074	T
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-1.1	T
PhyloP100		6.0
PrimateAI	Uncertain	0.78	T
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.24
Sift	Benign	0.081	T
Sift4G	Uncertain	0.014	D
Vest4		0.41
MVP		0.26
ClinPred		0.20	T
GERP RS		5.3
gMVP		0.58
Mutation Taster		=68/32	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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;