chr5-668207-C-G

Variant names:

• chr5-668207-C-G
• rs79129291
• NM_007030.3:c.312-2084G>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_007030.3(TPPP):​c.312-2084G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.0016 (4 hom., cov: 14)
• Consequence: TPPP NM_007030.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -5.21
• Publications: 0 publications found

Genes affected

TPPP (HGNC:24164): (tubulin polymerization promoting protein) Enables several functions, including GTPase activity; magnesium ion binding activity; and protein homodimerization activity. Involved in several processes, including microtubule cytoskeleton organization; negative regulation of tubulin deacetylation; and positive regulation of protein polymerization. Located in several cellular components, including mitochondrion; mitotic spindle; and perinuclear region of cytoplasm. Colocalizes with microtubule and microtubule bundle. [provided by Alliance of Genome Resources, Apr 2022]

CEP72 (HGNC:25547): (centrosomal protein 72) The product of this gene is a member of the leucine-rich-repeat (LRR) superfamily of proteins. The protein is localized to the centrosome, a non-membraneous organelle that functions as the major microtubule-organizing center in animal cells. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BP6: Variant 5-668207-C-G is Benign according to our data. Variant chr5-668207-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2655251.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007030.3. 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
	TPPP	NM_007030.3	MANE Select	c.312-2084G>C		intron	N/A	NP_008961.1	O94811
	CEP72	NR_164122.1		n.3938C>G		non_coding_transcript_exon	Exon 16 of 16

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TPPP	ENST00000360578.7	TSL:1 MANE Select	c.312-2084G>C		intron	N/A	ENSP00000353785.5	O94811
	TPPP	ENST00000889051.1		c.312-2084G>C		intron	N/A	ENSP00000559110.1
	TPPP	ENST00000889052.1		c.312-2084G>C		intron	N/A	ENSP00000559111.1

Frequencies

GnomAD3 genomes AF: 0.00158 AC: 147 AN: 93170 Hom.: 4 Cov.: 14

Gnomad AFR AF: 0.00498

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00162

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00262

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000885

Gnomad OTH AF: 0.000775

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.00158 AC: 147 AN: 93200 Hom.: 4 Cov.: 14 AF XY: 0.00142 AC XY: 64 AN XY: 45054

African (AFR) AF: 0.00497 AC: 120 AN: 24124

American (AMR) AF: 0.00162 AC: 15 AN: 9272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2292

East Asian (EAS) AF: 0.00263 AC: 7 AN: 2658

South Asian (SAS) AF: 0.00 AC: 0 AN: 2268

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5500

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 116

European-Non Finnish (NFE) AF: 0.0000885 AC: 4 AN: 45190

Other (OTH) AF: 0.000766 AC: 1 AN: 1306

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.064
DANN	Benign	0.16
PhyloP100		-5.2
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.16		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: rs79129291; hg19: chr5-668322;