chr9-130911810-T-C

Position:

• chr9-130911810-T-C

Variant summary

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

The NM_032843.5(FIBCD1):​c.928A>G​(p.Thr310Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,451,256 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: FIBCD1 NM_032843.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.75

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 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FIBCD1	NM_032843.5	c.928A>G	p.Thr310Ala	missense_variant	5/7	ENST00000372338.9	NP_116232.3
FIBCD1	NM_001145106.2	c.928A>G	p.Thr310Ala	missense_variant	6/8		NP_001138578.1
FIBCD1	XM_047423989.1	c.928A>G	p.Thr310Ala	missense_variant	6/8		XP_047279945.1
FIBCD1	XM_047423990.1	c.454A>G	p.Thr152Ala	missense_variant	5/7		XP_047279946.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FIBCD1	ENST00000372338.9	c.928A>G	p.Thr310Ala	missense_variant	5/7	1	NM_032843.5	ENSP00000361413.4
FIBCD1	ENST00000448616.5	c.928A>G	p.Thr310Ala	missense_variant	6/8	5		ENSP00000414501.1
FIBCD1	ENST00000444139.5	c.787A>G	p.Thr263Ala	missense_variant	4/5	2		ENSP00000395319.1
FIBCD1	ENST00000372337.6	c.454A>G	p.Thr152Ala	missense_variant	5/7	5		ENSP00000361412.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1451256 Hom.: 0 Cov.: 30 AF XY: 0.00000139 AC XY: 1 AN XY: 721212

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000514

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

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

Mar 16, 2024

The c.928A>G (p.T310A) alteration is located in exon 5 (coding exon 5) of the FIBCD1 gene. This alteration results from a A to G substitution at nucleotide position 928, causing the threonine (T) at amino acid position 310 to be replaced by an alanine (A). 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	0.11
BayesDel_addAF	Uncertain	0.021	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.022	T;T;.
Eigen	Benign	-0.18
Eigen_PC	Benign	-0.056
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.83	T;.;T
M_CAP	Uncertain	0.14	D
MetaRNN	Uncertain	0.47	T;T;T
MetaSVM	Benign	-0.65	T
MutationAssessor	Benign	0.97	L;L;.
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-1.9	N;N;N
REVEL	Uncertain	0.41
Sift	Benign	0.13	T;T;T
Sift4G	Benign	0.70	T;T;T
Polyphen		0.24	B;B;.
Vest4		0.56
MutPred		0.45		Loss of phosphorylation at T310 (P = 0.043);Loss of phosphorylation at T310 (P = 0.043);.;
MVP		0.75
MPC		0.34
ClinPred		0.67	D
GERP RS		4.0
Varity_R		0.46
gMVP		0.35

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

LitVar

Other links and lift over

dbSNP: rs1832055875; hg19: chr9-133787197;