4-16163413-G-A

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_153365.3(TAPT1):c.1599C>T(p.Asp533=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0114 in 1,613,744 control chromosomes in the GnomAD database, including 152 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0069 (14 hom., cov: 32)
  • Exomes 𝑓: 0.012 (138 hom.)
• Consequence: TAPT1 NM_153365.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.02

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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 4-16163413-G-A is Benign according to our data. Variant chr4-16163413-G-A is described in ClinVar as [Benign]. Clinvar id is 719092.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-16163413-G-A is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-1.02 with no splicing effect.
• BS2: High Homozygotes in GnomAd at 14 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TAPT1	NM_153365.3	c.1599C>T	p.Asp533=	synonymous_variant	14/14	ENST00000405303.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TAPT1	ENST00000405303.7	c.1599C>T	p.Asp533=	synonymous_variant	14/14	1	NM_153365.3	P1

Frequencies

GnomAD3 genomes AF: 0.00690 AC: 1049 AN: 152002 Hom.: 14 Cov.: 32

Gnomad AFR AF: 0.00247

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.00367

Gnomad ASJ AF: 0.000577

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00704

Gnomad FIN AF: 0.00436

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0117

Gnomad OTH AF: 0.00335

GnomAD3 exomes AF: 0.00741 AC: 1847 AN: 249232 Hom.: 13 AF XY: 0.00767 AC XY: 1037 AN XY: 135208

Gnomad AFR exome AF: 0.00181

Gnomad AMR exome AF: 0.00310

Gnomad ASJ exome AF: 0.00189

Gnomad EAS exome AF: 0.0000556

Gnomad SAS exome AF: 0.00422

Gnomad FIN exome AF: 0.00659

Gnomad NFE exome AF: 0.0122

Gnomad OTH exome AF: 0.00661

GnomAD4 exome AF: 0.0119 AC: 17322 AN: 1461624 Hom.: 138 Cov.: 31 AF XY: 0.0117 AC XY: 8497 AN XY: 727100

Gnomad4 AFR exome AF: 0.00173

Gnomad4 AMR exome AF: 0.00320

Gnomad4 ASJ exome AF: 0.00149

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00420

Gnomad4 FIN exome AF: 0.00747

Gnomad4 NFE exome AF: 0.0142

Gnomad4 OTH exome AF: 0.00898

GnomAD4 genome AF: 0.00690 AC: 1049 AN: 152120 Hom.: 14 Cov.: 32 AF XY: 0.00640 AC XY: 476 AN XY: 74354

Gnomad4 AFR AF: 0.00246

Gnomad4 AMR AF: 0.00366

Gnomad4 ASJ AF: 0.000577

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00705

Gnomad4 FIN AF: 0.00436

Gnomad4 NFE AF: 0.0117

Gnomad4 OTH AF: 0.00331

Alfa AF: 0.00589 Hom.: 0

Bravo AF: 0.00692

Asia WGS AF: 0.00231 AC: 9 AN: 3478

EpiCase AF: 0.0116

EpiControl AF: 0.00966

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 30, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 15, 2020	- -

TAPT1-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 19, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
Cadd	Benign	1.0
Dann	Benign	0.38

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: rs34007466; hg19: chr4-16165036;