chr5-14143754-CCCCCGCCGCGTCCTCCGG-C

Position:

• chr5-14143754-CCCCCGCCGCGTCCTCCGG-C

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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.96

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]

ACMG classification

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	Protein	UniProt
TRIO	NM_007118.4	c.40_57del	p.Ser14_Ala19del	inframe_deletion	1/57	ENST00000344204.9	NP_009049.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIO	ENST00000344204.9	c.40_57del	p.Ser14_Ala19del	inframe_deletion	1/57	1	NM_007118.4	ENSP00000339299	P1
TRIO	ENST00000698541.1	c.40_57del	p.Ser14_Ala19del	inframe_deletion	1/37			ENSP00000513786
TRIO	ENST00000502816.1	n.64_81del		non_coding_transcript_exon_variant	1/5	2
TRIO	ENST00000505971.5	n.64_81del		non_coding_transcript_exon_variant	1/4	3

Frequencies

GnomAD3 genomes AF: 0.0000274 AC: 4 AN: 145892 Hom.: 0 Cov.: 31

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: 2 AN: 842974 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 390414

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: 4 AN: 145892 Hom.: 0 Cov.: 31 AF XY: 0.0000564 AC XY: 4 AN XY: 70908

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.: 0

Bravo AF: 0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1227649681; hg19: chr5-14143863;