3-133400315-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_003571.4(BFSP2):c.232C>A(p.Leu78Ile) 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 Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: BFSP2 NM_003571.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.70

Genes affected

BFSP2 (HGNC:1041): (beaded filament structural protein 2) More than 99% of the vertebrate ocular lens is comprised of terminally differentiated lens fiber cells. Two lens-specific intermediate filament-like proteins, the protein product of this gene (phakinin), and filensin, are expressed only after fiber cell differentiation has begun. Both proteins are found in a structurally unique cytoskeletal element that is referred to as the beaded filament (BF). Mutations in this gene have been associated with juvenile-onset, progressive cataracts and Dowling-Meara epidermolysis bullosa simplex. [provided by RefSeq, Jun 2009]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BFSP2	NM_003571.4	c.232C>A	p.Leu78Ile	missense_variant	1/7	ENST00000302334.3
BFSP2	XM_017007315.2	c.232C>A	p.Leu78Ile	missense_variant	1/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BFSP2	ENST00000302334.3	c.232C>A	p.Leu78Ile	missense_variant	1/7	1	NM_003571.4	P1
BFSP2	ENST00000513441.1	n.242C>A		non_coding_transcript_exon_variant	1/2	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 17, 2021

The c.232C>A (p.L78I) alteration is located in exon 1 (coding exon 1) of the BFSP2 gene. This alteration results from a C to A substitution at nucleotide position 232, causing the leucine (L) at amino acid position 78 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Uncertain	0.054	T
BayesDel_noAF	Benign	-0.16
Cadd	Uncertain	23
Dann	Uncertain	1.0
DEOGEN2	Benign	0.26	T
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.067	D
MetaRNN	Uncertain	0.53	D
MetaSVM	Uncertain	0.12	D
MutationAssessor	Uncertain	2.5	M
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-0.50	N
REVEL	Uncertain	0.55
Sift	Benign	0.12	T
Sift4G	Uncertain	0.044	D
Polyphen		1.0	D
Vest4		0.56
MutPred		0.57		Loss of methylation at R76 (P = 0.1283);
MVP		0.76
MPC		0.68
ClinPred		0.88	D
GERP RS		4.2
Varity_R		0.087
gMVP		0.28

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-133119159;