4-16166623-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_153365.3(TAPT1):c.1474+10G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0248 in 1,611,980 control chromosomes in the GnomAD database, including 577 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.021 (48 hom., cov: 32)
  • Exomes 𝑓: 0.025 (529 hom.)
• Consequence: TAPT1 NM_153365.3 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0830

Genes affected

TAPT1 (HGNC:26887): (transmembrane anterior posterior transformation 1) This gene encodes a highly conserved protein that localizes to the centrosome and/or ciliary basal body. Mutations in this gene disrupt Golgi morphology and trafficking and normal primary cilium formation and these mutations are congenitally manifested by severe undermineralization of the intra-uterine skeleton. A mutation in the mouse ortholog of this gene results in homeotic, posterior-to-anterior transformations of the axial skeleton which are similar to the phenotype of mouse homeobox C8 gene mutants. In mouse, this gene is thought to function downstream of homeobox C8 to transduce extracellular patterning information during axial skeleton development. [provided by RefSeq, Jan 2017]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP6: Variant 4-16166623-C-T is Benign according to our data. Variant chr4-16166623-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1207054.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-16166623-C-T is described in Lovd as [Benign].
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0214 (3257/152276) while in subpopulation AMR AF= 0.0268 (410/15300). AF 95% confidence interval is 0.0247. There are 48 homozygotes in gnomad4. There are 1516 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 47 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TAPT1	NM_153365.3	c.1474+10G>A		intron_variant		ENST00000405303.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TAPT1	ENST00000405303.7	c.1474+10G>A		intron_variant		1	NM_153365.3	P1

Frequencies

GnomAD3 genomes AF: 0.0214 AC: 3249 AN: 152158 Hom.: 47 Cov.: 32

Gnomad AFR AF: 0.0141

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.0269

Gnomad ASJ AF: 0.0380

Gnomad EAS AF: 0.0121

Gnomad SAS AF: 0.0112

Gnomad FIN AF: 0.0176

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0257

Gnomad OTH AF: 0.0268

GnomAD3 exomes AF: 0.0222 AC: 5534 AN: 249028 Hom.: 77 AF XY: 0.0221 AC XY: 2984 AN XY: 135098

Gnomad AFR exome AF: 0.0147

Gnomad AMR exome AF: 0.0202

Gnomad ASJ exome AF: 0.0350

Gnomad EAS exome AF: 0.0100

Gnomad SAS exome AF: 0.0138

Gnomad FIN exome AF: 0.0199

Gnomad NFE exome AF: 0.0273

Gnomad OTH exome AF: 0.0247

GnomAD4 exome AF: 0.0251 AC: 36680 AN: 1459704 Hom.: 529 Cov.: 31 AF XY: 0.0249 AC XY: 18081 AN XY: 725772

Gnomad4 AFR exome AF: 0.0149

Gnomad4 AMR exome AF: 0.0201

Gnomad4 ASJ exome AF: 0.0376

Gnomad4 EAS exome AF: 0.0236

Gnomad4 SAS exome AF: 0.0150

Gnomad4 FIN exome AF: 0.0185

Gnomad4 NFE exome AF: 0.0264

Gnomad4 OTH exome AF: 0.0264

GnomAD4 genome AF: 0.0214 AC: 3257 AN: 152276 Hom.: 48 Cov.: 32 AF XY: 0.0204 AC XY: 1516 AN XY: 74450

Gnomad4 AFR AF: 0.0142

Gnomad4 AMR AF: 0.0268

Gnomad4 ASJ AF: 0.0380

Gnomad4 EAS AF: 0.0121

Gnomad4 SAS AF: 0.0108

Gnomad4 FIN AF: 0.0176

Gnomad4 NFE AF: 0.0257

Gnomad4 OTH AF: 0.0299

Alfa AF: 0.0221 Hom.: 12

Bravo AF: 0.0221

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 09, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 30, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
Cadd	Benign	9.0
Dann	Benign	0.85
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs2271748; hg19: chr4-16168246; COSMIC: COSV58823475; COSMIC: COSV58823475;