chr20-17531223-GC-AA

Variant names:

• chr20-17531223-GC-AA
• rs886038419
• NM_001195.5:c.106_107delGCinsTT

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP6

The NM_001195.5(BFSP1):​c.106_107delGCinsTT​(p.Ala36Phe) variant causes a missense 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 Conflicting classifications of pathogenicity (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: BFSP1 NM_001195.5 missense
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:2
• Conservation: PhyloP100: 0.793

Genes affected

BFSP1 (HGNC:1040): (beaded filament structural protein 1) This gene encodes a lens-specific intermediate filament-like protein named filensin. The encoded protein is expressed in lens fiber cells after differentiation has begun. This protein functions as a component of the beaded filament which is a cytoskeletal structure found in lens fiber cells. Mutations in this gene are the cause of autosomal recessive cortical juvenile-onset cataract. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 20-17531223-GC-AA is Benign according to our data. Variant chr20-17531223-GC-AA is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 257613.We mark this variant Likely_benign, oryginal submissions are: {Benign=2, Uncertain_significance=1}.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BFSP1	NM_001195.5	c.106_107delGCinsTT	p.Ala36Phe	missense_variant		ENST00000377873.8	NP_001186.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BFSP1	ENST00000377873.8	c.106_107delGCinsTT	p.Ala36Phe	missense_variant		1	NM_001195.5	ENSP00000367104.3
BFSP1	ENST00000377868.6	c.3-6316_3-6315delGCinsTT		intron_variant	Intron 1 of 7	1		ENSP00000367099.2
BFSP1	ENST00000536626.7	c.-40-6316_-40-6315delGCinsTT		intron_variant	Intron 2 of 8	2		ENSP00000442522.1
BFSP1	ENST00000473415.1	n.472-6316_472-6315delGCinsTT		intron_variant	Intron 4 of 6	3

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1 Benign:2

Revision: criteria provided, conflicting classifications

Submissions by phenotype

not provided Uncertain:1

Feb 05, 2021

GeneDx

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Cataract 33 Benign:1

Jul 10, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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: rs886038419; hg19: chr20-17511868; COSMIC: COSV105309564;