rs730882197

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5

The NM_020374.4(FERRY3):​c.639_640insACAA​(p.Gln214ThrfsTer31) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: not found (cov: 32)

Consequence

FERRY3
NM_020374.4 frameshift

Scores

Not classified

Clinical Significance

Pathogenic/Likely pathogenic no assertion criteria provided P:2

Conservation

PhyloP100: 0.550
Variant links:
Genes affected
FERRY3 (HGNC:1184): (FERRY endosomal RAB5 effector complex subunit 3) This gene is highly conserved from nematodes to humans. In rat, the orthologous gene encodes a cytoplasmic protein that is involved in mast cell degranulation. The human gene has been implicated in autosomal recessive intellectual disability. [provided by RefSeq, Sep 2016]

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ACMG classification

Classification made for transcript

Verdict is Pathogenic. Variant got 11 ACMG points.

PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 12-4525342-G-GTTGT is Pathogenic according to our data. Variant chr12-4525342-G-GTTGT is described in ClinVar as [Likely_pathogenic]. Clinvar id is 183276.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FERRY3NM_020374.4 linkc.639_640insACAA p.Gln214ThrfsTer31 frameshift_variant Exon 6 of 14 ENST00000261250.8 NP_065107.1 Q9NQ89

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
C12orf4ENST00000261250.8 linkc.639_640insACAA p.Gln214ThrfsTer31 frameshift_variant Exon 6 of 14 1 NM_020374.4 ENSP00000261250.3 Q9NQ89

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Pathogenic/Likely pathogenic
Submissions summary: Pathogenic:2
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Hypotonia;C1263846:Attention deficit hyperactivity disorder;C3714756:Intellectual disability Pathogenic:1
Dec 01, 2014
Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre
Significance: Likely pathogenic
Review Status: no assertion criteria provided
Collection Method: research

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Intellectual disability, autosomal recessive 66 Pathogenic:1
Jan 13, 2015
OMIM
Significance: Pathogenic
Review Status: no assertion criteria provided
Collection Method: literature only

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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.

Other links and lift over

dbSNP: rs730882197; hg19: chr12-4634508; API