19-4311985-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_024333.3(FSD1):​c.634C>T​(p.Arg212Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000105 in 1,613,276 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

FSD1
NM_024333.3 missense

Scores

3
14
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.62
Variant links:
Genes affected
FSD1 (HGNC:13745): (fibronectin type III and SPRY domain containing 1) This gene encodes a centrosome associated protein that is characterized by an N-terminal coiled-coil region downstream of B-box (BBC) domain, a central fibronectin type III domain, and a C-terminal repeats in splA and RyR (SPRY) domain. The encoded protein associates with a subset of microtubules and may be involved in the stability and organization of microtubules during cytokinesis. [provided by RefSeq, Apr 2009]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.845

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FSD1NM_024333.3 linkc.634C>T p.Arg212Cys missense_variant Exon 7 of 13 ENST00000221856.11 NP_077309.1 Q9BTV5
FSD1NM_001330429.2 linkc.634C>T p.Arg212Cys missense_variant Exon 7 of 13 NP_001317358.1 M0R366

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FSD1ENST00000221856.11 linkc.634C>T p.Arg212Cys missense_variant Exon 7 of 13 1 NM_024333.3 ENSP00000221856.5 Q9BTV5

Frequencies

GnomAD3 genomes
AF:
0.0000526
AC:
8
AN:
152222
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000482
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000327
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000120
AC:
3
AN:
249518
Hom.:
0
AF XY:
0.0000222
AC XY:
3
AN XY:
135226
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000290
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0000479
Gnomad NFE exome
AF:
0.00000886
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000616
AC:
9
AN:
1461054
Hom.:
0
Cov.:
32
AF XY:
0.00000963
AC XY:
7
AN XY:
726832
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.0000190
Gnomad4 NFE exome
AF:
0.00000450
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000526
AC:
8
AN:
152222
Hom.:
0
Cov.:
32
AF XY:
0.0000941
AC XY:
7
AN XY:
74368
show subpopulations
Gnomad4 AFR
AF:
0.0000482
Gnomad4 AMR
AF:
0.000327
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000264
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Aug 15, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.634C>T (p.R212C) alteration is located in exon 7 (coding exon 7) of the FSD1 gene. This alteration results from a C to T substitution at nucleotide position 634, causing the arginine (R) at amino acid position 212 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
Uncertain
0.45
BayesDel_addAF
Uncertain
0.095
D
BayesDel_noAF
Uncertain
-0.020
CADD
Pathogenic
30
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.26
T;T
Eigen
Uncertain
0.55
Eigen_PC
Uncertain
0.46
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Uncertain
0.96
D;D
M_CAP
Uncertain
0.18
D
MetaRNN
Pathogenic
0.85
D;D
MetaSVM
Uncertain
0.0067
D
MutationAssessor
Pathogenic
3.1
M;.
PrimateAI
Uncertain
0.69
T
PROVEAN
Uncertain
-3.6
D;.
REVEL
Uncertain
0.62
Sift
Uncertain
0.011
D;.
Sift4G
Uncertain
0.0020
D;D
Polyphen
1.0
D;.
Vest4
0.84
MVP
0.42
MPC
1.6
ClinPred
0.96
D
GERP RS
3.6
Varity_R
0.31
gMVP
0.66

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: rs376221601; hg19: chr19-4311982; COSMIC: COSV55694892; COSMIC: COSV55694892; API