9-130904147-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_032843.5(FIBCD1):​c.1303G>A​(p.Val435Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000347 in 1,613,420 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000034 ( 0 hom. )

Consequence

FIBCD1
NM_032843.5 missense

Scores

7
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.313
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.24569798).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FIBCD1NM_032843.5 linkc.1303G>A p.Val435Met missense_variant Exon 7 of 7 ENST00000372338.9 NP_116232.3 Q8N539-1
FIBCD1NM_001145106.2 linkc.1303G>A p.Val435Met missense_variant Exon 8 of 8 NP_001138578.1 Q8N539-1
FIBCD1XM_047423989.1 linkc.1303G>A p.Val435Met missense_variant Exon 8 of 8 XP_047279945.1
FIBCD1XM_047423990.1 linkc.829G>A p.Val277Met missense_variant Exon 7 of 7 XP_047279946.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FIBCD1ENST00000372338.9 linkc.1303G>A p.Val435Met missense_variant Exon 7 of 7 1 NM_032843.5 ENSP00000361413.4 Q8N539-1
FIBCD1ENST00000448616.5 linkc.1303G>A p.Val435Met missense_variant Exon 8 of 8 5 ENSP00000414501.1 Q8N539-1
FIBCD1ENST00000372337.6 linkc.829G>A p.Val277Met missense_variant Exon 7 of 7 5 ENSP00000361412.1 A3KFJ8
FIBCD1ENST00000444139.5 linkc.806-75G>A intron_variant Intron 4 of 4 2 ENSP00000395319.1 H0Y4Y8

Frequencies

GnomAD3 genomes
AF:
0.0000460
AC:
7
AN:
152206
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.0000941
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000588
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000439
AC:
11
AN:
250750
Hom.:
0
AF XY:
0.0000442
AC XY:
6
AN XY:
135724
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000289
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000109
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000619
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.0000335
AC:
49
AN:
1461214
Hom.:
0
Cov.:
33
AF XY:
0.0000275
AC XY:
20
AN XY:
726884
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000101
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000315
Gnomad4 OTH exome
AF:
0.0000662
GnomAD4 genome
AF:
0.0000460
AC:
7
AN:
152206
Hom.:
0
Cov.:
33
AF XY:
0.0000404
AC XY:
3
AN XY:
74340
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.0000941
Gnomad4 NFE
AF:
0.0000588
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000533
Hom.:
0
Bravo
AF:
0.0000378
ExAC
AF:
0.0000577
AC:
7
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Mar 07, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1303G>A (p.V435M) alteration is located in exon 7 (coding exon 7) of the FIBCD1 gene. This alteration results from a G to A substitution at nucleotide position 1303, causing the valine (V) at amino acid position 435 to be replaced by a methionine (M). 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
Uncertain
0.37
BayesDel_addAF
Benign
-0.18
T
BayesDel_noAF
Benign
-0.26
CADD
Benign
19
DANN
Uncertain
1.0
DEOGEN2
Benign
0.031
T;T;.
Eigen
Benign
-0.29
Eigen_PC
Benign
-0.21
FATHMM_MKL
Benign
0.31
N
LIST_S2
Uncertain
0.95
D;.;D
M_CAP
Uncertain
0.10
D
MetaRNN
Benign
0.25
T;T;T
MetaSVM
Benign
-0.47
T
MutationAssessor
Benign
1.5
L;L;.
PrimateAI
Uncertain
0.54
T
PROVEAN
Benign
-2.1
N;N;N
REVEL
Uncertain
0.31
Sift
Benign
0.055
T;T;D
Sift4G
Uncertain
0.021
D;D;D
Polyphen
0.25
B;B;.
Vest4
0.25
MVP
0.72
MPC
0.51
ClinPred
0.15
T
GERP RS
1.3
Varity_R
0.21
gMVP
0.44

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs766248349; hg19: chr9-133779534; COSMIC: COSV104582040; API