Genetic Variant FYTTD1:p.Cys242Phe (chr3-197776995-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_032288.7(FYTTD1):c.725G>T(p.Cys242Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000069 in 1,448,256 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C242Y) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

FYTTD1
NM_032288.7 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.609

Publications

0 publications found

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]

FYTTD1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.15599906).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032288.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FYTTD1	NM_032288.7	MANE Select	c.725G>T	p.Cys242Phe	missense	Exon 7 of 9	NP_115664.2
FYTTD1	NM_001011537.3		c.647G>T	p.Cys216Phe	missense	Exon 8 of 10	NP_001011537.2	Q96QD9-2
FYTTD1	NR_027840.2		n.1198G>T		non_coding_transcript_exon	Exon 7 of 9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FYTTD1	ENST00000241502.9	TSL:1 MANE Select	c.725G>T	p.Cys242Phe	missense	Exon 7 of 9	ENSP00000241502.3	Q96QD9-1
FYTTD1	ENST00000966386.1		c.821G>T	p.Cys274Phe	missense	Exon 8 of 10	ENSP00000636445.1
FYTTD1	ENST00000966385.1		c.719G>T	p.Cys240Phe	missense	Exon 7 of 9	ENSP00000636444.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.90e-7

AC:

AN:

1448256

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

720830

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33062

American (AMR)

AF:

0.00

AC:

AN:

43786

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25972

East Asian (EAS)

AF:

0.00

AC:

AN:

39608

South Asian (SAS)

AF:

0.00

AC:

AN:

84652

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53370

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5742

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1102148

Other (OTH)

AF:

0.0000167

AC:

AN:

59916

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.43

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.034

Eigen

Benign

-0.29

Eigen_PC

Benign

-0.28

FATHMM_MKL

Benign

0.25

LIST_S2

Benign

0.76

M_CAP

Benign

0.019

MetaRNN

Benign

0.16

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

PhyloP100

0.61

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-0.89

REVEL

Benign

0.045

Sift

Benign

0.053

Sift4G

Benign

0.18

Polyphen

0.76

Vest4

0.28

MutPred

0.51

Loss of catalytic residue at V244 (P = 0.118)

MVP

0.068

MPC

0.60

ClinPred

0.29

GERP RS

1.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.14

gMVP

0.17

Mutation Taster

=95/5

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over