20-63555850-C-T

Variant summary

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

The NM_001319152.2(FNDC11):​c.187C>T​(p.Arg63Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000397 in 1,613,016 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 34)
Exomes 𝑓: 0.000040 ( 0 hom. )

Consequence

FNDC11
NM_001319152.2 missense

Scores

4
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.533
Variant links:
Genes affected
FNDC11 (HGNC:28764): (fibronectin type III domain containing 11)

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=0.17885485).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FNDC11NM_001319152.2 linkc.187C>T p.Arg63Cys missense_variant Exon 2 of 2 ENST00000370097.2 NP_001306081.1 Q9BVV2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FNDC11ENST00000370097.2 linkc.187C>T p.Arg63Cys missense_variant Exon 2 of 2 2 NM_001319152.2 ENSP00000359115.1 Q9BVV2
FNDC11ENST00000370098.4 linkc.187C>T p.Arg63Cys missense_variant Exon 2 of 2 1 ENSP00000359116.3 Q9BVV2
FNDC11ENST00000615526.1 linkc.187C>T p.Arg63Cys missense_variant Exon 1 of 1 6 ENSP00000480914.1 Q9BVV2
FNDC11ENST00000611891.1 linkc.187C>T p.Arg63Cys missense_variant Exon 2 of 2 3 ENSP00000483577.1 A0A087X0Q0

Frequencies

GnomAD3 genomes
AF:
0.0000394
AC:
6
AN:
152258
Hom.:
0
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.0000965
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000320
AC:
8
AN:
249782
Hom.:
0
AF XY:
0.0000295
AC XY:
4
AN XY:
135368
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000289
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000620
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000397
AC:
58
AN:
1460758
Hom.:
0
Cov.:
76
AF XY:
0.0000303
AC XY:
22
AN XY:
726720
show subpopulations
Gnomad4 AFR exome
AF:
0.0000597
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000450
Gnomad4 OTH exome
AF:
0.0000497
GnomAD4 genome
AF:
0.0000394
AC:
6
AN:
152258
Hom.:
0
Cov.:
34
AF XY:
0.0000403
AC XY:
3
AN XY:
74380
show subpopulations
Gnomad4 AFR
AF:
0.0000965
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000115
Hom.:
0
Bravo
AF:
0.0000416
ExAC
AF:
0.0000330
AC:
4
Asia WGS
AF:
0.000577
AC:
2
AN:
3478
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Nov 09, 2021
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.187C>T (p.R63C) alteration is located in exon 2 (coding exon 1) of the FNDC11 gene. This alteration results from a C to T substitution at nucleotide position 187, causing the arginine (R) at amino acid position 63 to be replaced by a cysteine (C). 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
0.20
BayesDel_addAF
Benign
-0.052
T
BayesDel_noAF
Benign
-0.16
CADD
Benign
19
DANN
Uncertain
1.0
DEOGEN2
Benign
0.30
.;T;T;T
Eigen
Uncertain
0.32
Eigen_PC
Uncertain
0.31
FATHMM_MKL
Benign
0.67
D
LIST_S2
Benign
0.76
T;.;.;T
M_CAP
Benign
0.014
T
MetaRNN
Benign
0.18
T;T;T;T
MetaSVM
Benign
-0.76
T
PROVEAN
Benign
-2.1
.;N;.;N
REVEL
Benign
0.17
Sift
Benign
0.092
.;T;.;T
Sift4G
Uncertain
0.0020
D;D;D;D
Polyphen
1.0
.;D;D;D
Vest4
0.31, 0.17, 0.31
MVP
0.42
MPC
0.31
ClinPred
0.37
T
GERP RS
4.4
Varity_R
0.095
gMVP
0.49

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: rs758808516; hg19: chr20-62187203; API