chr19-48965317-GCGGTCCCGCGGGTCTGTCTCTTGCTTCAA-G

Position:

• chr19-48965317-GCGGTCCCGCGGGTCTGTCTCTTGCTTCAA-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP5

The NM_000146.4(FTL):​c.-189_-161del variant causes a 5 prime UTR 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 Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: FTL NM_000146.4 5_prime_UTR
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 2.19

Genes affected

FTL (HGNC:3999): (ferritin light chain) This gene encodes the light subunit of the ferritin protein. Ferritin is the major intracellular iron storage protein in prokaryotes and eukaryotes. It is composed of 24 subunits of the heavy and light ferritin chains. Variation in ferritin subunit composition may affect the rates of iron uptake and release in different tissues. A major function of ferritin is the storage of iron in a soluble and nontoxic state. Defects in this light chain ferritin gene are associated with several neurodegenerative diseases and hyperferritinemia-cataract syndrome. This gene has multiple pseudogenes. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 19-48965317-GCGGTCCCGCGGGTCTGTCTCTTGCTTCAA-G is Pathogenic according to our data. Variant chr19-48965317-GCGGTCCCGCGGGTCTGTCTCTTGCTTCAA-G is described in ClinVar as [Pathogenic]. Clinvar id is 16478.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr19-48965317-GCGGTCCCGCGGGTCTGTCTCTTGCTTCAA-G is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FTL	NM_000146.4	c.-189_-161del		5_prime_UTR_variant	1/4	ENST00000331825.11	NP_000137.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FTL	ENST00000331825.11	c.-189_-161del		5_prime_UTR_variant	1/4	1	NM_000146.4	ENSP00000366525	P1

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

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Hereditary hyperferritinemia with congenital cataracts Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Feb 19, 2013

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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: rs1555796939; hg19: chr19-49468574;