13-87677903-GAG-AAA

Variant names:

• chr13-87677903-GAG-AAA
• NM_001384609.1:c.2515_2517delGAGinsAAA
• SLITRK5 p.Glu839Lys

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM5 PP3

The NM_001384609.1(SLITRK5):​c.2515_2517delGAGinsAAA​(p.Glu839Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E839D) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLITRK5 NM_001384609.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.97
• Publications: 0 publications found

Genes affected

SLITRK5 (HGNC:20295): (SLIT and NTRK like family member 5) Members of the SLITRK family, such as SLITRK5, are integral membrane proteins with 2 N-terminal leucine-rich repeat (LRR) domains similar to those of SLIT proteins (see SLIT1; MIM 603742). Most SLITRKs, including SLITRK5, also have C-terminal regions that share homology with neurotrophin receptors (see NTRK1; MIM 191315). SLITRKs are expressed predominantly in neural tissues and have neurite-modulating activity (Aruga et al., 2003 [PubMed 14557068]).[supplied by OMIM, Mar 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM5: Other missense variant is known to change same aminoacid residue: Variant chr13-87677903-G-C is described in ClinVar as Likely_pathogenic. ClinVar VariationId is 402167.Status of the report is criteria_provided_single_submitter, 1 stars.
• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001384609.1. 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
	SLITRK5	NM_001384609.1	MANE Select	c.2515_2517delGAGinsAAA	p.Glu839Lys	missense	N/A	NP_001371538.1	O94991-1
	SLITRK5	NM_001384610.1		c.2515_2517delGAGinsAAA	p.Glu839Lys	missense	N/A	NP_001371539.1	O94991-1
	SLITRK5	NM_015567.2		c.2515_2517delGAGinsAAA	p.Glu839Lys	missense	N/A	NP_056382.1	O94991-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLITRK5	ENST00000683689.1	MANE Select	c.2515_2517delGAGinsAAA	p.Glu839Lys	missense	N/A	ENSP00000508338.1	O94991-1
	SLITRK5	ENST00000325089.7	TSL:1	c.2515_2517delGAGinsAAA	p.Glu839Lys	missense	N/A	ENSP00000366283.2	O94991-1
	SLITRK5	ENST00000933099.1		c.2515_2517delGAGinsAAA	p.Glu839Lys	missense	N/A	ENSP00000603158.1

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		8.0

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr13-88330158;