4-16163565-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_153365.3(TAPT1):c.1475-28C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000943 in 1,535,264 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0044 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00056 (6 hom.)
• Consequence: TAPT1 NM_153365.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.06

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 4-16163565-G-A is Benign according to our data. Variant chr4-16163565-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1191410.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TAPT1	NM_153365.3	c.1475-28C>T		intron_variant		ENST00000405303.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TAPT1	ENST00000405303.7	c.1475-28C>T		intron_variant		1	NM_153365.3	P1

Frequencies

GnomAD3 genomes AF: 0.00434 AC: 661 AN: 152156 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.0142

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00327

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.00430

GnomAD3 exomes AF: 0.00132 AC: 278 AN: 211278 Hom.: 3 AF XY: 0.00104 AC XY: 118 AN XY: 113800

Gnomad AFR exome AF: 0.0152

Gnomad AMR exome AF: 0.00123

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000116

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000279

Gnomad OTH exome AF: 0.00113

GnomAD4 exome AF: 0.000565 AC: 781 AN: 1382990 Hom.: 6 Cov.: 23 AF XY: 0.000499 AC XY: 344 AN XY: 688960

Gnomad4 AFR exome AF: 0.0156

Gnomad4 AMR exome AF: 0.00151

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000492

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000137

Gnomad4 OTH exome AF: 0.00139

GnomAD4 genome AF: 0.00438 AC: 667 AN: 152274 Hom.: 1 Cov.: 32 AF XY: 0.00404 AC XY: 301 AN XY: 74444

Gnomad4 AFR AF: 0.0143

Gnomad4 AMR AF: 0.00327

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000162

Gnomad4 OTH AF: 0.00425

Alfa AF: 0.000677 Hom.: 0

Bravo AF: 0.00508

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 29, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	15
Dann	Benign	0.54

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs114552336; hg19: chr4-16165188;