Variant 7-100155498-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_018275.5(TRAPPC14):c.1396-43T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.556 in 1,516,426 control chromosomes in the GnomAD database, including 235,195 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.54 ( 22341 hom., cov: 33)

Exomes 𝑓: 0.56 ( 212854 hom. )

Consequence

TRAPPC14
NM_018275.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0190

Variant links:

Genes affected

TRAPPC14 (HGNC:25604): (trafficking protein particle complex subunit 14) Enables alpha-tubulin binding activity. Involved in cilium assembly and regulation of cell population proliferation. Located in several cellular components, including microtubule cytoskeleton; midbody; and plasma membrane. Part of TRAPPII protein complex. Implicated in primary autosomal recessive microcephaly. [provided by Alliance of Genome Resources, Apr 2022]

TRAPPC14 links:

LAMTOR4 (HGNC:33772): (late endosomal/lysosomal adaptor, MAPK and MTOR activator 4) Contributes to guanyl-nucleotide exchange factor activity and molecular adaptor activity. Involved in several processes, including cellular response to amino acid stimulus; positive regulation of TOR signaling; and protein localization to lysosome. Located in lysosome. Part of Ragulator complex. [provided by Alliance of Genome Resources, Apr 2022]

LAMTOR4 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=-0.9).

BP6

Variant 7-100155498-A-G is Benign according to our data. Variant chr7-100155498-A-G is described in ClinVar as [Benign]. Clinvar id is 1192633.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.624 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRAPPC14	NM_018275.5 linkuse as main transcript	c.1396-43T>C		intron_variant		ENST00000316937.8	NP_060745.3
TRAPPC14	NM_001303470.2 linkuse as main transcript	c.589-43T>C		intron_variant			NP_001290399.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRAPPC14	ENST00000316937.8 linkuse as main transcript	c.1396-43T>C		intron_variant		1	NM_018275.5	ENSP00000324741	P1	Q8WVR3-1

Frequencies

GnomAD3 genomes

AF:

0.540

AC:

82076

AN:

151932

Hom.:

22314

Cov.:

show subpopulations

Gnomad AFR

AF:

0.507

Gnomad AMI

AF:

0.654

Gnomad AMR

AF:

0.466

Gnomad ASJ

AF:

0.624

Gnomad EAS

AF:

0.641

Gnomad SAS

AF:

0.598

Gnomad FIN

AF:

0.572

Gnomad MID

AF:

0.598

Gnomad NFE

AF:

0.554

Gnomad OTH

AF:

0.545

GnomAD3 exomes

AF:

0.555

AC:

87997

AN:

158412

Hom.:

24238

AF XY:

0.562

AC XY:

47023

AN XY:

83712

show subpopulations

Gnomad AFR exome

AF:

0.514

Gnomad AMR exome

AF:

0.468

Gnomad ASJ exome

AF:

0.631

Gnomad EAS exome

AF:

0.650

Gnomad SAS exome

AF:

0.599

Gnomad FIN exome

AF:

0.572

Gnomad NFE exome

AF:

0.553

Gnomad OTH exome

AF:

0.562

GnomAD4 exome

AF:

0.558

AC:

761154

AN:

1364376

Hom.:

212854

Cov.:

AF XY:

0.561

AC XY:

375196

AN XY:

669216

show subpopulations

Gnomad4 AFR exome

AF:

0.509

Gnomad4 AMR exome

AF:

0.468

Gnomad4 ASJ exome

AF:

0.614

Gnomad4 EAS exome

AF:

0.608

Gnomad4 SAS exome

AF:

0.600

Gnomad4 FIN exome

AF:

0.561

Gnomad4 NFE exome

AF:

0.555

Gnomad4 OTH exome

AF:

0.562

GnomAD4 genome

AF:

0.540

AC:

82161

AN:

152050

Hom.:

22341

Cov.:

AF XY:

0.543

AC XY:

40342

AN XY:

74330

show subpopulations

Gnomad4 AFR

AF:

0.507

Gnomad4 AMR

AF:

0.467

Gnomad4 ASJ

AF:

0.624

Gnomad4 EAS

AF:

0.642

Gnomad4 SAS

AF:

0.599

Gnomad4 FIN

AF:

0.572

Gnomad4 NFE

AF:

0.554

Gnomad4 OTH

AF:

0.545

Alfa

AF:

0.534

Hom.:

3390

Bravo

AF:

0.533

Asia WGS

AF:

0.620

AC:

2157

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Microcephaly 25, primary, autosomal recessive

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

5.8

DANN

Benign

0.54

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