3-197776997-C-T

Variant summary

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

The NM_032288.7(FYTTD1):​c.727C>T​(p.Pro243Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000163 in 1,597,994 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

FYTTD1
NM_032288.7 missense

Scores

1
5
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.48
Variant links:
Genes affected
FYTTD1 (HGNC:25407): (forty-two-three domain containing 1) Enables mRNA binding activity. Involved in mRNA export from nucleus. Located in nuclear speck. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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 rank MANE Protein UniProt
FYTTD1NM_032288.7 linkc.727C>T p.Pro243Ser missense_variant Exon 7 of 9 ENST00000241502.9 NP_115664.2 Q96QD9-1A0A024R9K4
FYTTD1NM_001011537.3 linkc.649C>T p.Pro217Ser missense_variant Exon 8 of 10 NP_001011537.2 Q96QD9-2
FYTTD1NR_027840.2 linkn.1200C>T non_coding_transcript_exon_variant Exon 7 of 9

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FYTTD1ENST00000241502.9 linkc.727C>T p.Pro243Ser missense_variant Exon 7 of 9 1 NM_032288.7 ENSP00000241502.3 Q96QD9-1

Frequencies

GnomAD3 genomes
AF:
0.0000724
AC:
11
AN:
151904
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000722
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000607
AC:
15
AN:
246954
Hom.:
0
AF XY:
0.0000600
AC XY:
8
AN XY:
133304
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000329
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:
0.0000356
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000104
AC:
15
AN:
1446090
Hom.:
0
Cov.:
27
AF XY:
0.0000111
AC XY:
8
AN XY:
719814
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000251
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000363
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000724
AC:
11
AN:
151904
Hom.:
0
Cov.:
31
AF XY:
0.0000944
AC XY:
7
AN XY:
74180
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000722
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.000125
ExAC
AF:
0.0000412
AC:
5

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
May 31, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.727C>T (p.P243S) alteration is located in exon 7 (coding exon 7) of the FYTTD1 gene. This alteration results from a C to T substitution at nucleotide position 727, causing the proline (P) at amino acid position 243 to be replaced by a serine (S). 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
0.083
BayesDel_addAF
Benign
-0.31
T
BayesDel_noAF
Benign
-0.38
CADD
Benign
21
DANN
Uncertain
0.99
DEOGEN2
Benign
0.088
.;.;T;.
Eigen
Benign
-0.011
Eigen_PC
Benign
0.19
FATHMM_MKL
Uncertain
0.97
D
LIST_S2
Benign
0.83
T;T;T;T
M_CAP
Benign
0.0065
T
MetaRNN
Uncertain
0.44
T;D;D;D
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.59
.;.;N;.
PrimateAI
Uncertain
0.49
T
PROVEAN
Uncertain
-4.3
D;N;N;D
REVEL
Benign
0.12
Sift
Benign
0.044
D;T;T;T
Sift4G
Pathogenic
0.0
D;T;T;T
Polyphen
0.14, 0.074
.;B;B;.
Vest4
0.17, 0.17, 0.17
MutPred
0.88
.;.;Gain of sheet (P = 0.039);.;
MVP
0.068
MPC
0.20
ClinPred
0.24
T
GERP RS
4.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.16
gMVP
0.31

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: rs746678476; hg19: chr3-197503868; API