5-14143754-CCCCCGCCGCGTCCTCCGG-CCCCCGCCGCGTCCTCCGGCCCCGCCGCGTCCTCCGG

Variant names:

• chr5-14143754-C-CCCCCGCCGCGTCCTCCGG
• rs1227649681
• NM_007118.4:c.40_57dupTCCTCCGGCCCCGCCGCG

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PM4

The NM_007118.4(TRIO):​c.40_57dupTCCTCCGGCCCCGCCGCG​(p.Ser14_Ala19dup) variant causes a conservative inframe insertion change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: TRIO NM_007118.4 conservative_inframe_insertion
• Clinical Significance: Not reported in ClinVar
• 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_007118.4.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIO	NM_007118.4	c.40_57dupTCCTCCGGCCCCGCCGCG	p.Ser14_Ala19dup	conservative_inframe_insertion	Exon 1 of 57	ENST00000344204.9	NP_009049.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRIO	ENST00000344204.9	c.40_57dupTCCTCCGGCCCCGCCGCG	p.Ser14_Ala19dup	conservative_inframe_insertion	Exon 1 of 57	1	NM_007118.4	ENSP00000339299.4
TRIO	ENST00000698541.1	c.40_57dupTCCTCCGGCCCCGCCGCG	p.Ser14_Ala19dup	conservative_inframe_insertion	Exon 1 of 37			ENSP00000513786.1
TRIO	ENST00000502816.1	n.64_81dupTCCTCCGGCCCCGCCGCG		non_coding_transcript_exon_variant	Exon 1 of 5	2
TRIO	ENST00000505971.5	n.64_81dupTCCTCCGGCCCCGCCGCG		non_coding_transcript_exon_variant	Exon 1 of 4	3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

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;