X-151722682-C-A

Variant summary

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

The NM_033085.3(FATE1):​c.475C>A​(p.Arg159Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000638 in 1,097,798 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R159H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 25)
Exomes 𝑓: 0.0000064 ( 0 hom. 1 hem. )

Consequence

FATE1
NM_033085.3 missense

Scores

1
1
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.759
Variant links:
Genes affected
FATE1 (HGNC:24683): (fetal and adult testis expressed 1) This gene encodes a cancer-testis antigen that is highly expressed in hepatocellular carcinomas and other tumors and weakly expressed in normal tissues except testis. The protein is strongly expressed in spermatogonia, primary spermatocytes, and Sertoli cells in seminiferous tubules. This protein may have a role in the control of early testicular differentiation and cell proliferation. [provided by RefSeq, Jan 2010]

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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=0.14200014).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FATE1NM_033085.3 linkc.475C>A p.Arg159Ser missense_variant Exon 5 of 5 ENST00000370350.7 NP_149076.1 Q969F0

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FATE1ENST00000370350.7 linkc.475C>A p.Arg159Ser missense_variant Exon 5 of 5 1 NM_033085.3 ENSP00000359375.3 Q969F0
FATE1ENST00000417321.1 linkc.*101C>A 3_prime_UTR_variant Exon 4 of 4 3 ENSP00000400493.1 H7C1I5

Frequencies

GnomAD3 genomes
Cov.:
25
GnomAD3 exomes
AF:
0.0000165
AC:
3
AN:
181784
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
66934
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
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:
0.0000372
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000638
AC:
7
AN:
1097798
Hom.:
0
Cov.:
30
AF XY:
0.00000275
AC XY:
1
AN XY:
363206
show subpopulations
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:
0.00000831
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
25
Bravo
AF:
0.00000378
ExAC
AF:
0.0000165
AC:
2

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Feb 22, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.475C>A (p.R159S) alteration is located in exon 5 (coding exon 5) of the FATE1 gene. This alteration results from a C to A substitution at nucleotide position 475, causing the arginine (R) at amino acid position 159 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
Uncertain
0.49
BayesDel_addAF
Benign
-0.44
T
BayesDel_noAF
Benign
-0.75
CADD
Benign
10
DANN
Benign
0.94
DEOGEN2
Benign
0.048
T
FATHMM_MKL
Benign
0.069
N
LIST_S2
Benign
0.50
T
M_CAP
Pathogenic
0.38
D
MetaRNN
Benign
0.14
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.4
L
PrimateAI
Benign
0.22
T
PROVEAN
Benign
-1.9
N
REVEL
Benign
0.038
Sift
Benign
0.054
T
Sift4G
Benign
0.082
T
Polyphen
0.92
P
Vest4
0.068
MutPred
0.25
Loss of MoRF binding (P = 0.0367);
MVP
0.82
MPC
0.15
ClinPred
0.36
T
GERP RS
-0.76
Varity_R
0.37
gMVP
0.43

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs777906779; hg19: chrX-150891154; API