rs321096

Variant names:

• chr5-700878-A-G
• rs321096
• XM_024454346.1:c.-238T>C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The XM_024454346.1(TPPP):​c.-238T>C variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00616 in 151,740 control chromosomes in the GnomAD database, including 3 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 0.0062 (3 hom., cov: 35)
• Consequence: TPPP XM_024454346.1 upstream_gene
• Clinical Significance: Not reported in ClinVar
• 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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TPPP	XM_024454346.1	c.-238T>C		upstream_gene_variant			XP_024310114.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.00617 AC: 936 AN: 151624 Hom.: 3 Cov.: 35

Gnomad AFR AF: 0.00143

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00362

Gnomad ASJ AF: 0.00520

Gnomad EAS AF: 0.00213

Gnomad SAS AF: 0.000625

Gnomad FIN AF: 0.0200

Gnomad MID AF: 0.00637

Gnomad NFE AF: 0.00840

Gnomad OTH AF: 0.00335

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

GnomAD4 genome AF: 0.00616 AC: 935 AN: 151740 Hom.: 3 Cov.: 35 AF XY: 0.00628 AC XY: 466 AN XY: 74190

Gnomad4 AFR AF: 0.00142

Gnomad4 AMR AF: 0.00361

Gnomad4 ASJ AF: 0.00520

Gnomad4 EAS AF: 0.00213

Gnomad4 SAS AF: 0.000417

Gnomad4 FIN AF: 0.0200

Gnomad4 NFE AF: 0.00839

Gnomad4 OTH AF: 0.00427

Alfa AF: 0.0110 Hom.: 1

Asia WGS AF: 0.00867 AC: 30 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.9
DANN	Benign	0.25

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs321096; hg19: chr5-700993;