5-665261-C-T

Variant names:

• chr5-665261-C-T
• rs140456348
• NM_007030.3:c.501G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_007030.3(TPPP):​c.501G>A​(p.Thr167Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00316 in 1,613,612 control chromosomes in the GnomAD database, including 157 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0060 (31 hom., cov: 32)
  • Exomes 𝑓: 0.0029 (126 hom.)
• Consequence: TPPP NM_007030.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.96
• Publications: 2 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP6: Variant 5-665261-C-T is Benign according to our data. Variant chr5-665261-C-T is described in ClinVar as Benign. ClinVar VariationId is 771367.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.96 with no splicing effect.
• BA1: GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0666 is higher than 0.05.

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.501G>A	p.Thr167Thr	synonymous	Exon 4 of 4	NP_008961.1	O94811
	CEP72	NR_164122.1		n.2530C>T		non_coding_transcript_exon	Exon 15 of 16

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TPPP	ENST00000360578.7	TSL:1 MANE Select	c.501G>A	p.Thr167Thr	synonymous	Exon 4 of 4	ENSP00000353785.5	O94811
	TPPP	ENST00000889051.1		c.501G>A	p.Thr167Thr	synonymous	Exon 5 of 5	ENSP00000559110.1
	TPPP	ENST00000889052.1		c.501G>A	p.Thr167Thr	synonymous	Exon 4 of 4	ENSP00000559111.1

Frequencies

GnomAD3 genomes AF: 0.00591 AC: 899 AN: 152042 Hom.: 28 Cov.: 32

Gnomad AFR AF: 0.000459

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0509

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0120

Gnomad SAS AF: 0.000829

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000235

Gnomad OTH AF: 0.0101

GnomAD2 exomes AF: 0.0112 AC: 2793 AN: 250066 AF XY: 0.00873

Gnomad AFR exome AF: 0.000495

Gnomad AMR exome AF: 0.0743

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00735

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000221

Gnomad OTH exome AF: 0.00772

GnomAD4 exome AF: 0.00287 AC: 4196 AN: 1461452 Hom.: 126 Cov.: 33 AF XY: 0.00251 AC XY: 1827 AN XY: 727012

African (AFR) AF: 0.000418 AC: 14 AN: 33478

American (AMR) AF: 0.0686 AC: 3065 AN: 44668

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.0195 AC: 775 AN: 39688

South Asian (SAS) AF: 0.000603 AC: 52 AN: 86238

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53188

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5764

European-Non Finnish (NFE) AF: 0.000102 AC: 113 AN: 1111916

Other (OTH) AF: 0.00291 AC: 176 AN: 60386

GnomAD4 genome AF: 0.00599 AC: 911 AN: 152160 Hom.: 31 Cov.: 32 AF XY: 0.00672 AC XY: 500 AN XY: 74372

African (AFR) AF: 0.000458 AC: 19 AN: 41516

American (AMR) AF: 0.0512 AC: 782 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.0120 AC: 62 AN: 5154

South Asian (SAS) AF: 0.000830 AC: 4 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000235 AC: 16 AN: 67994

Other (OTH) AF: 0.0133 AC: 28 AN: 2110

Alfa AF: 0.00130 Hom.: 1

Bravo AF: 0.00920

Asia WGS AF: 0.0160 AC: 56 AN: 3478

EpiCase AF: 0.000273

EpiControl AF: 0.000237

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	1.9
DANN	Benign	0.82
PhyloP100		-2.0
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs140456348; hg19: chr5-665376;