Variant 5-14143754-CCCCCGCCGCGTCCTCCGG-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM4

The NM_007118.4(TRIO):c.40_57del(p.Ser14_Ala19del) variant causes a inframe deletion change. The variant allele was found at a frequency of 0.00000607 in 988,866 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000024 ( 0 hom. )

Consequence

TRIO
NM_007118.4 inframe_deletion

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.96

Variant links:

Genes affected

TRIO (HGNC:12303): (trio Rho guanine nucleotide exchange factor) This gene encodes a large protein that functions as a GDP to GTP exchange factor. This protein promotes the reorganization of the actin cytoskeleton, thereby playing a role in cell migration and growth. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]

TRIO links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_007118.4.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRIO	NM_007118.4 linkuse as main transcript	c.40_57del	p.Ser14_Ala19del	inframe_deletion	1/57	ENST00000344204.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRIO	ENST00000344204.9 linkuse as main transcript	c.40_57del	p.Ser14_Ala19del	inframe_deletion	1/57	1	NM_007118.4	P1	O75962-1
TRIO	ENST00000698541.1 linkuse as main transcript	c.40_57del	p.Ser14_Ala19del	inframe_deletion	1/37
TRIO	ENST00000502816.1 linkuse as main transcript	n.64_81del		non_coding_transcript_exon_variant	1/5	2
TRIO	ENST00000505971.5 linkuse as main transcript	n.64_81del		non_coding_transcript_exon_variant	1/4	3

Frequencies

GnomAD3 genomes

AF:

0.0000274

AC:

AN:

145892

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000241

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000305

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000237

AC:

AN:

842974

Hom.:

AF XY:

0.00

AC XY:

AN XY:

390414

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000260

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000274

AC:

AN:

145892

Hom.:

Cov.:

AF XY:

0.0000564

AC XY:

AN XY:

70908

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000241

Gnomad4 NFE

AF:

0.0000305

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 20, 2023

The c.40_57del18 (p.S14_A19del) alteration is located in exon 1 (coding exon 1) of the TRIO gene. This alteration consists of an in-frame deletion of 18 nucleotides between nucleotide positions c.40 and c.57, resulting in the deletion of <NA> residues. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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