3-197773479-C-T

Variant names:

• chr3-197773479-C-T
• rs1330477850
• NM_032288.7:c.574C>T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_032288.7(FYTTD1):​c.574C>T​(p.Leu192Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000139 in 1,440,550 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: FYTTD1 NM_032288.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.49

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.76

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FYTTD1	NM_032288.7	c.574C>T	p.Leu192Phe	missense_variant	Exon 5 of 9	ENST00000241502.9	NP_115664.2
FYTTD1	NM_001011537.3	c.496C>T	p.Leu166Phe	missense_variant	Exon 6 of 10		NP_001011537.2
FYTTD1	NR_027840.2	n.1047C>T		non_coding_transcript_exon_variant	Exon 5 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FYTTD1	ENST00000241502.9	c.574C>T	p.Leu192Phe	missense_variant	Exon 5 of 9	1	NM_032288.7	ENSP00000241502.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000139 AC: 2 AN: 1440550 Hom.: 0 Cov.: 27 AF XY: 0.00000140 AC XY: 1 AN XY: 716034

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 0.00000182

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 01, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.574C>T (p.L192F) alteration is located in exon 5 (coding exon 5) of the FYTTD1 gene. This alteration results from a C to T substitution at nucleotide position 574, causing the leucine (L) at amino acid position 192 to be replaced by a phenylalanine (F). 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	Pathogenic	0.64
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.060
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.049	.;.;T;.
Eigen	Uncertain	0.23
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.91	D;T;T;T
M_CAP	Benign	0.013	T
MetaRNN	Pathogenic	0.76	D;D;D;D
MetaSVM	Benign	-0.71	T
MutationAssessor	Benign	1.7	.;.;L;.
PrimateAI	Uncertain	0.69	T
PROVEAN	Uncertain	-2.5	N;N;N;N
REVEL	Benign	0.27
Sift	Benign	0.076	T;T;T;T
Sift4G	Benign	0.16	T;T;T;T
Polyphen		1.0, 0.0030	.;D;B;.
Vest4		0.50, 0.50, 0.51
MutPred		0.81		.;.;Gain of sheet (P = 0.0827);.;
MVP		0.22
MPC		0.62
ClinPred		0.91	D
GERP RS		5.1
Varity_R		0.22
gMVP		0.30

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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

Other links and lift over

dbSNP: rs1330477850; hg19: chr3-197500350;