rs386057

Variant names:

• chr5-685633-G-A
• rs386057
• NM_007030.3:c.-4-7569C>T

Your query was ambiguous. Multiple possible variants found:

• chr5-685633-G-A
• chr5-685633-G-C
• chr5-685633-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007030.3(TPPP):​c.-4-7569C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.387 in 152,140 control chromosomes in the GnomAD database, including 11,526 homozygotes. 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: 𝑓 0.39 (11526 hom., cov: 34)
• Consequence: TPPP NM_007030.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.88
• Publications: 9 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.544 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TPPP	NM_007030.3	c.-4-7569C>T		intron_variant	Intron 1 of 3	ENST00000360578.7	NP_008961.1
TPPP	XM_024454346.1	c.-4-7569C>T		intron_variant	Intron 1 of 3		XP_024310114.1
TPPP	XM_047416674.1	c.-5+6928C>T		intron_variant	Intron 2 of 4		XP_047272630.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TPPP	ENST00000360578.7	c.-4-7569C>T		intron_variant	Intron 1 of 3	1	NM_007030.3	ENSP00000353785.5

Frequencies

GnomAD3 genomes AF: 0.387 AC: 58842 AN: 152022 Hom.: 11516 Cov.: 34

Gnomad AFR AF: 0.361

Gnomad AMI AF: 0.375

Gnomad AMR AF: 0.436

Gnomad ASJ AF: 0.391

Gnomad EAS AF: 0.561

Gnomad SAS AF: 0.392

Gnomad FIN AF: 0.370

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.379

Gnomad OTH AF: 0.420

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

GnomAD4 genome AF: 0.387 AC: 58895 AN: 152140 Hom.: 11526 Cov.: 34 AF XY: 0.388 AC XY: 28886 AN XY: 74384

African (AFR) AF: 0.361 AC: 15000 AN: 41504

American (AMR) AF: 0.436 AC: 6668 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.391 AC: 1357 AN: 3468

East Asian (EAS) AF: 0.561 AC: 2901 AN: 5170

South Asian (SAS) AF: 0.392 AC: 1893 AN: 4830

European-Finnish (FIN) AF: 0.370 AC: 3929 AN: 10606

Middle Eastern (MID) AF: 0.483 AC: 142 AN: 294

European-Non Finnish (NFE) AF: 0.379 AC: 25775 AN: 67948

Other (OTH) AF: 0.420 AC: 888 AN: 2116

Alfa AF: 0.386 Hom.: 18548

Bravo AF: 0.396

Asia WGS AF: 0.466 AC: 1619 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.56
DANN	Benign	0.36
PhyloP100		-2.9
Mutation Taster		=100/0	polymorphism (auto)

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: rs386057; hg19: chr5-685748;