NM_153365.3:c.1474+302G>A

Variant names:

• chr4-16166331-C-T
• rs2271749
• NM_153365.3:c.1474+302G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_153365.3(TAPT1):​c.1474+302G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0432 in 152,274 control chromosomes in the GnomAD database, including 245 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.043 (245 hom., cov: 32)
• Consequence: TAPT1 NM_153365.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.122
• Publications: 3 publications found

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 Gene-Disease associations (from GenCC):

• complex lethal osteochondrodysplasia

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, G2P, Orphanet
• cataract

  Inheritance: AR Classification: LIMITED Submitted by: G2P

ENSG00000296956 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 4-16166331-C-T is Benign according to our data. Variant chr4-16166331-C-T is described in ClinVar as Benign. ClinVar VariationId is 1268825.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0872 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153365.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAPT1	NM_153365.3	MANE Select	c.1474+302G>A		intron	N/A	NP_699196.2	Q6NXT6-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAPT1	ENST00000405303.7	TSL:1 MANE Select	c.1474+302G>A		intron	N/A	ENSP00000385347.2	Q6NXT6-1
	TAPT1	ENST00000963923.1		c.1468+302G>A		intron	N/A	ENSP00000633982.1
	TAPT1	ENST00000963924.1		c.1405+302G>A		intron	N/A	ENSP00000633983.1

Frequencies

GnomAD3 genomes AF: 0.0431 AC: 6555 AN: 152156 Hom.: 243 Cov.: 32

Gnomad AFR AF: 0.0896

Gnomad AMI AF: 0.00440

Gnomad AMR AF: 0.0342

Gnomad ASJ AF: 0.0433

Gnomad EAS AF: 0.0117

Gnomad SAS AF: 0.0116

Gnomad FIN AF: 0.0176

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0258

Gnomad OTH AF: 0.0444

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

GnomAD4 genome AF: 0.0432 AC: 6571 AN: 152274 Hom.: 245 Cov.: 32 AF XY: 0.0407 AC XY: 3028 AN XY: 74456

African (AFR) AF: 0.0896 AC: 3722 AN: 41528

American (AMR) AF: 0.0341 AC: 522 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0433 AC: 150 AN: 3468

East Asian (EAS) AF: 0.0118 AC: 61 AN: 5182

South Asian (SAS) AF: 0.0112 AC: 54 AN: 4828

European-Finnish (FIN) AF: 0.0176 AC: 187 AN: 10614

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0258 AC: 1758 AN: 68030

Other (OTH) AF: 0.0473 AC: 100 AN: 2116

Alfa AF: 0.0271 Hom.: 43

Bravo AF: 0.0469

Asia WGS AF: 0.0170 AC: 59 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.1
DANN	Benign	0.63
PhyloP100		-0.12
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs2271749; hg19: chr4-16167954;