Variant chr4-16166623-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

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

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.0830

Variant links:

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]

TAPT1 links:

TAPT1 (HGNC:):

TAPT1 links:

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ACMG classification

Classification made for transcript

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 GnomAd4 at 48 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAPT1	NM_153365.3 linkuse as main transcript	c.1474+10G>A		intron_variant		ENST00000405303.7	NP_699196.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAPT1	ENST00000405303.7 linkuse as main transcript	c.1474+10G>A		intron_variant		1	NM_153365.3	ENSP00000385347.2		Q6NXT6-1

Frequencies

GnomAD3 genomes

AF:

0.0214

AC:

3249

AN:

152158

Hom.:

Cov.:

show subpopulations

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.:

AF XY:

0.0221

AC XY:

2984

AN XY:

135098

show subpopulations

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.:

AF XY:

0.0249

AC XY:

18081

AN XY:

725772

show subpopulations

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.:

Cov.:

AF XY:

0.0204

AC XY:

1516

AN XY:

74450

show subpopulations

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.:

Bravo

AF:

0.0221

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 09, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over