9-130904080-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_032843.5(FIBCD1):c.1370T>G(p.Val457Gly) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: FIBCD1 NM_032843.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.78

Genes affected

FIBCD1 (HGNC:25922): (fibrinogen C domain containing 1) FIBCD1 is a conserved type II transmembrane endocytic receptor that binds chitin and is located primarily in the intestinal brush border (Schlosser et al., 2009 [PubMed 19710473]).[supplied by OMIM, Apr 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.36834496).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FIBCD1	NM_032843.5	c.1370T>G	p.Val457Gly	missense_variant	7/7	ENST00000372338.9
FIBCD1	NM_001145106.2	c.1370T>G	p.Val457Gly	missense_variant	8/8
FIBCD1	XM_047423989.1	c.1370T>G	p.Val457Gly	missense_variant	8/8
FIBCD1	XM_047423990.1	c.896T>G	p.Val299Gly	missense_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FIBCD1	ENST00000372338.9	c.1370T>G	p.Val457Gly	missense_variant	7/7	1	NM_032843.5	P1
FIBCD1	ENST00000448616.5	c.1370T>G	p.Val457Gly	missense_variant	8/8	5		P1
FIBCD1	ENST00000372337.6	c.896T>G	p.Val299Gly	missense_variant	7/7	5
FIBCD1	ENST00000444139.5	c.808-8T>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

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

Dec 07, 2021

The c.1370T>G (p.V457G) alteration is located in exon 7 (coding exon 7) of the FIBCD1 gene. This alteration results from a T to G substitution at nucleotide position 1370, causing the valine (V) at amino acid position 457 to be replaced by a glycine (G). 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	0.065
BayesDel_addAF	Uncertain	0.064	T
BayesDel_noAF	Benign	-0.15
Cadd	Benign	22
Dann	Uncertain	0.99
DEOGEN2	Benign	0.032	T;T;.
Eigen	Benign	-0.018
Eigen_PC	Benign	0.043
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.70	T;.;T
M_CAP	Uncertain	0.25	D
MetaRNN	Benign	0.37	T;T;T
MetaSVM	Benign	-0.30	T
MutationAssessor	Uncertain	2.0	M;M;.
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.93	N;N;N
REVEL	Uncertain	0.32
Sift	Pathogenic	0.0	D;D;D
Sift4G	Uncertain	0.0020	D;D;D
Polyphen		0.25	B;B;.
Vest4		0.26
MutPred		0.55		Loss of stability (P = 0.0194);Loss of stability (P = 0.0194);.;
MVP		0.83
MPC		0.33
ClinPred		0.89	D
GERP RS		3.5
Varity_R		0.55
gMVP		0.48

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: chr9-133779467;