5-666129-G-GGGGCACAGGCGACTTA

Position:

• chr5-666129-G-GGGGCACAGGCGACTTA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_007030.3(TPPP):​c.312-7_312-6insTAAGTCGCCTGTGCCC variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.309 in 1,605,486 control chromosomes in the GnomAD database, including 78,558 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.32 (7949 hom., cov: 0)
  • Exomes 𝑓: 0.31 (70609 hom.)
• Consequence: TPPP NM_007030.3 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: 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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 5-666129-G-GGGGCACAGGCGACTTA is Benign according to our data. Variant chr5-666129-G-GGGGCACAGGCGACTTA is described in ClinVar as [Benign]. Clinvar id is 2116070.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.372 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TPPP	NM_007030.3	c.312-7_312-6insTAAGTCGCCTGTGCCC		splice_region_variant, splice_polypyrimidine_tract_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_312-6insTAAGTCGCCTGTGCCC		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_007030.3	ENSP00000353785	P1
CEP72	ENST00000514507.1	n.592+35_592+50dup		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.322 AC: 48546 AN: 150950 Hom.: 7941 Cov.: 0

Gnomad AFR AF: 0.377

Gnomad AMI AF: 0.280

Gnomad AMR AF: 0.372

Gnomad ASJ AF: 0.350

Gnomad EAS AF: 0.240

Gnomad SAS AF: 0.385

Gnomad FIN AF: 0.205

Gnomad MID AF: 0.343

Gnomad NFE AF: 0.296

Gnomad OTH AF: 0.319

GnomAD4 exome AF: 0.308 AC: 447741 AN: 1454420 Hom.: 70609 Cov.: 38 AF XY: 0.309 AC XY: 223573 AN XY: 723588

Gnomad4 AFR exome AF: 0.385

Gnomad4 AMR exome AF: 0.398

Gnomad4 ASJ exome AF: 0.340

Gnomad4 EAS exome AF: 0.250

Gnomad4 SAS exome AF: 0.390

Gnomad4 FIN exome AF: 0.209

Gnomad4 NFE exome AF: 0.300

Gnomad4 OTH exome AF: 0.318

GnomAD4 genome AF: 0.322 AC: 48587 AN: 151066 Hom.: 7949 Cov.: 0 AF XY: 0.320 AC XY: 23580 AN XY: 73802

Gnomad4 AFR AF: 0.376

Gnomad4 AMR AF: 0.373

Gnomad4 ASJ AF: 0.350

Gnomad4 EAS AF: 0.240

Gnomad4 SAS AF: 0.382

Gnomad4 FIN AF: 0.205

Gnomad4 NFE AF: 0.296

Gnomad4 OTH AF: 0.321

Alfa AF: 0.301 Hom.: 1144

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 18, 2024

- -

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: rs57043325; hg19: chr5-666244;