9-130905255-C-T

Variant summary

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

The NM_032843.5(FIBCD1):c.1105G>A(p.Ala369Thr) 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. 12/21 in silico tools predict 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: 1.89

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=0.2705067).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FIBCD1	NM_032843.5	c.1105G>A	p.Ala369Thr	missense_variant	6/7	ENST00000372338.9
FIBCD1	NM_001145106.2	c.1105G>A	p.Ala369Thr	missense_variant	7/8
FIBCD1	XM_047423989.1	c.1105G>A	p.Ala369Thr	missense_variant	7/8
FIBCD1	XM_047423990.1	c.631G>A	p.Ala211Thr	missense_variant	6/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FIBCD1	ENST00000372338.9	c.1105G>A	p.Ala369Thr	missense_variant	6/7	1	NM_032843.5	P1
FIBCD1	ENST00000448616.5	c.1105G>A	p.Ala369Thr	missense_variant	7/8	5		P1
FIBCD1	ENST00000372337.6	c.631G>A	p.Ala211Thr	missense_variant	6/7	5
FIBCD1	ENST00000444139.5	c.808-1183G>A		intron_variant		2

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

Jul 20, 2021

The c.1105G>A (p.A369T) alteration is located in exon 6 (coding exon 6) of the FIBCD1 gene. This alteration results from a G to A substitution at nucleotide position 1105, causing the alanine (A) at amino acid position 369 to be replaced by a threonine (T). 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	0.069
BayesDel_addAF	Benign	-0.017	T
BayesDel_noAF	Benign	-0.26
Cadd	Benign	22
Dann	Uncertain	1.0
DEOGEN2	Benign	0.022	T;T;.
Eigen	Benign	-0.092
Eigen_PC	Benign	0.069
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Uncertain	0.90	D;.;D
M_CAP	Uncertain	0.093	D
MetaRNN	Benign	0.27	T;T;T
MetaSVM	Benign	-0.37	T
MutationAssessor	Benign	0.15	N;N;.
MutationTaster	Benign	0.91	D;D;D;D
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-1.1	N;N;N
REVEL	Uncertain	0.34
Sift	Uncertain	0.029	D;D;D
Sift4G	Uncertain	0.045	D;D;D
Polyphen		0.0010	B;B;.
Vest4		0.14
MutPred		0.58		Loss of helix (P = 0.0558);Loss of helix (P = 0.0558);.;
MVP		0.78
MPC		0.12
ClinPred		0.67	D
GERP RS		4.1
Varity_R		0.25
gMVP		0.51

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: chr9-133780642; COSMIC: COSV53392736;