5-666129-G-GGGGCACAGGCAGTCGACTTA

Position:

• chr5-666129-G-GGGGCACAGGCAGTCGACTTA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The ENST00000360578.7(TPPP):​c.312-7_312-6insTAAGTCGACTGCCTGTGCCC variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00182 in 1,606,800 control chromosomes in the GnomAD database, including 52 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0099 (30 hom., cov: 0)
  • Exomes 𝑓: 0.00098 (22 hom.)
• Consequence: TPPP ENST00000360578.7 splice_region, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.51

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]

CEP72 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 5-666129-G-GGGGCACAGGCAGTCGACTTA is Benign according to our data. Variant chr5-666129-G-GGGGCACAGGCAGTCGACTTA is described in ClinVar as [Likely_benign]. Clinvar id is 789473.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00985 (1490/151240) while in subpopulation AFR AF= 0.0347 (1428/41150). AF 95% confidence interval is 0.0332. There are 30 homozygotes in gnomad4. There are 682 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 30 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TPPP	NM_007030.3	c.312-7_312-6insTAAGTCGACTGCCTGTGCCC		splice_region_variant, intron_variant		ENST00000360578.7	NP_008961.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TPPP	ENST00000360578.7	c.312-7_312-6insTAAGTCGACTGCCTGTGCCC		splice_region_variant, intron_variant		1	NM_007030.3	ENSP00000353785.5
CEP72	ENST00000514507.1	n.592+40_592+41insAGTCGACTTAGGGCACAGGC		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.00983 AC: 1485 AN: 151124 Hom.: 30 Cov.: 0

Gnomad AFR AF: 0.0347

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00269

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000209

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000886

Gnomad OTH AF: 0.00673

GnomAD4 exome AF: 0.000985 AC: 1433 AN: 1455560 Hom.: 22 Cov.: 38 AF XY: 0.000870 AC XY: 630 AN XY: 724098

Gnomad4 AFR exome AF: 0.0352

Gnomad4 AMR exome AF: 0.00235

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000139

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000216

Gnomad4 OTH exome AF: 0.00176

GnomAD4 genome AF: 0.00985 AC: 1490 AN: 151240 Hom.: 30 Cov.: 0 AF XY: 0.00923 AC XY: 682 AN XY: 73896

Gnomad4 AFR AF: 0.0347

Gnomad4 AMR AF: 0.00269

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000209

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000886

Gnomad4 OTH AF: 0.00666

Alfa AF: 0.00134 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1554021107; hg19: chr5-666244;