chr20-17496947-C-G

Position:

• chr20-17496947-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001195.5(BFSP1):​c.1033G>C​(p.Gly345Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. 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. G345S) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: BFSP1 NM_001195.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.631

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.070652455).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BFSP1	NM_001195.5	c.1033G>C	p.Gly345Arg	missense_variant	7/8	ENST00000377873.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BFSP1	ENST00000377873.8	c.1033G>C	p.Gly345Arg	missense_variant	7/8	1	NM_001195.5	P1
BFSP1	ENST00000377868.6	c.658G>C	p.Gly220Arg	missense_variant	7/8	1
BFSP1	ENST00000536626.7	c.616G>C	p.Gly206Arg	missense_variant	8/9	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	0.022
DANN	Benign	0.51
DEOGEN2	Benign	0.045	T;.;.
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.066	N
LIST_S2	Benign	0.67	T;T;T
M_CAP	Benign	0.083	D
MetaRNN	Benign	0.071	T;T;T
MetaSVM	Benign	-0.72	T
MutationAssessor	Benign	1.1	L;.;.
MutationTaster	Benign	1.0	P;P;P;P
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.17	N;N;N
REVEL	Benign	0.014
Sift	Benign	0.56	T;T;T
Sift4G	Benign	0.65	T;.;T
Polyphen		0.0040	B;B;.
Vest4		0.13
MutPred		0.25		Gain of MoRF binding (P = 0.02);.;.;
MVP		0.51
MPC		0.34
ClinPred		0.092	T
GERP RS		-5.0
Varity_R		0.035
gMVP		0.21

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs6080719; hg19: chr20-17477592;