12-64836645-C-T

Variant names:

• chr12-64836645-C-T
• rs746992553
• NM_015279.2:c.750C>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_015279.2(TBC1D30):​c.750C>T​(p.Asn250Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000724 in 1,381,684 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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: 32)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: TBC1D30 NM_015279.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.96
• 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 -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).
• BP7: Synonymous conserved (PhyloP=1.96 with no splicing effect.

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.750C>T	p.Asn250Asn	synonymous	Exon 6 of 12	NP_056094.1	Q9Y2I9-2
	TBC1D30	NM_001330186.2		c.750C>T	p.Asn250Asn	synonymous	Exon 6 of 12	NP_001317115.1
	TBC1D30	NM_001330187.2		c.408C>T	p.Asn136Asn	synonymous	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.750C>T	p.Asn250Asn	synonymous	Exon 6 of 12	ENSP00000440207.1	Q9Y2I9-2
	TBC1D30	ENST00000542120.6	TSL:1	c.1239C>T	p.Asn413Asn	synonymous	Exon 7 of 13	ENSP00000440640.2	Q9Y2I9-1
	ENSG00000288591	ENST00000674281.1		n.408C>T		non_coding_transcript_exon	Exon 8 of 17	ENSP00000501395.1	F8VZ81

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.24e-7 AC: 1 AN: 1381684 Hom.: 0 Cov.: 30 AF XY: 0.00000147 AC XY: 1 AN XY: 681522

African (AFR) AF: 0.00 AC: 0 AN: 31550

American (AMR) AF: 0.00 AC: 0 AN: 35536

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25138

East Asian (EAS) AF: 0.00 AC: 0 AN: 35678

South Asian (SAS) AF: 0.00 AC: 0 AN: 79036

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33866

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5682

European-Non Finnish (NFE) AF: 9.28e-7 AC: 1 AN: 1077390

Other (OTH) AF: 0.00 AC: 0 AN: 57808

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	11
DANN	Benign	0.70
PhyloP100		2.0

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: rs746992553; hg19: chr12-65230425; COSMIC: COSV57486875; COSMIC: COSV57486875;